Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections
Identifieur interne : 001334 ( Pmc/Corpus ); précédent : 001333; suivant : 001335Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections
Auteurs : Mohammad Amin Behzadi ; Victor H. Leyva-GradoSource :
- Frontiers in Microbiology [ 1664-302X ] ; 2019.
Abstract
Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.
Url:
DOI: 10.3389/fmicb.2019.01327
PubMed: 31275265
PubMed Central: 6594388
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PMC:6594388Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections</title><author><name sortKey="Behzadi, Mohammad Amin" sort="Behzadi, Mohammad Amin" uniqKey="Behzadi M" first="Mohammad Amin" last="Behzadi">Mohammad Amin Behzadi</name></author><author><name sortKey="Leyva Grado, Victor H" sort="Leyva Grado, Victor H" uniqKey="Leyva Grado V" first="Victor H." last="Leyva-Grado">Victor H. Leyva-Grado</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31275265</idno><idno type="pmc">6594388</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594388</idno><idno type="RBID">PMC:6594388</idno><idno type="doi">10.3389/fmicb.2019.01327</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">001334</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001334</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections</title><author><name sortKey="Behzadi, Mohammad Amin" sort="Behzadi, Mohammad Amin" uniqKey="Behzadi M" first="Mohammad Amin" last="Behzadi">Mohammad Amin Behzadi</name></author><author><name sortKey="Leyva Grado, Victor H" sort="Leyva Grado, Victor H" uniqKey="Leyva Grado V" first="Victor H." last="Leyva-Grado">Victor H. Leyva-Grado</name></author></analytic><series><title level="j">Frontiers in Microbiology</title><idno type="eISSN">1664-302X</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abarca, K" uniqKey="Abarca K">K. Abarca</name></author><author><name sortKey="Jung, E" uniqKey="Jung E">E. Jung</name></author><author><name sortKey="Fernandez, P" uniqKey="Fernandez P">P. Fernández</name></author><author><name sortKey="Zhao, L" uniqKey="Zhao L">L. Zhao</name></author><author><name sortKey="Harris, B" uniqKey="Harris B">B. Harris</name></author><author><name sortKey="Connor, E M" uniqKey="Connor E">E. M. Connor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ackermann, M" uniqKey="Ackermann M">M. Ackermann</name></author><author><name sortKey="Alnajjar, S" uniqKey="Alnajjar S">S. Alnajjar</name></author><author><name sortKey="Larios Mora, A" uniqKey="Larios Mora A">A. Larios-Mora</name></author><author><name sortKey="Koul, A" uniqKey="Koul A">A. Koul</name></author><author><name sortKey="Rigaux, P" uniqKey="Rigaux P">P. Rigaux</name></author><author><name sortKey="Gallup, J" uniqKey="Gallup J">J. Gallup</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Ghamdi, M" uniqKey="Al Ghamdi M">M. Al Ghamdi</name></author><author><name sortKey="Alghamdi, K M" uniqKey="Alghamdi K">K. M. Alghamdi</name></author><author><name sortKey="Ghandoora, Y" uniqKey="Ghandoora Y">Y. Ghandoora</name></author><author><name sortKey="Alzahrani, A" uniqKey="Alzahrani A">A. Alzahrani</name></author><author><name sortKey="Salah, F" uniqKey="Salah F">F. Salah</name></author><author><name sortKey="Alsulami, A" uniqKey="Alsulami A">A. Alsulami</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alame, M M" uniqKey="Alame M">M. M. Alame</name></author><author><name sortKey="Massaad, E" uniqKey="Massaad E">E. Massaad</name></author><author><name sortKey="Zaraket, H" uniqKey="Zaraket H">H. Zaraket</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ali, S O" uniqKey="Ali S">S. O. Ali</name></author><author><name sortKey="Takas, T" uniqKey="Takas T">T. Takas</name></author><author><name sortKey="Nyborg, A" uniqKey="Nyborg A">A. Nyborg</name></author><author><name sortKey="Shoemaker, K" uniqKey="Shoemaker K">K. Shoemaker</name></author><author><name sortKey="Kallewaard, N L" uniqKey="Kallewaard N">N. L. Kallewaard</name></author><author><name sortKey="Chiong, R" uniqKey="Chiong R">R. Chiong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J. A. Al-Tawfiq</name></author><author><name sortKey="Alfaraj, S H" uniqKey="Alfaraj S">S. H. Alfaraj</name></author><author><name sortKey="Altuwaijri, T A" uniqKey="Altuwaijri T">T. A. Altuwaijri</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z. A. Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J. A. Al-Tawfiq</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z. A. Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J. A. Al-Tawfiq</name></author><author><name sortKey="Momattin, H" uniqKey="Momattin H">H. Momattin</name></author><author><name sortKey="Dib, J" uniqKey="Dib J">J. Dib</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z. A. Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amarelle, L" uniqKey="Amarelle L">L. Amarelle</name></author><author><name sortKey="Lecuona, E" uniqKey="Lecuona E">E. Lecuona</name></author><author><name sortKey="Sznajder, J I" uniqKey="Sznajder J">J. I. Sznajder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Antonini, T M" uniqKey="Antonini T">T. M. Antonini</name></author><author><name sortKey="Coilly, A" uniqKey="Coilly A">A. Coilly</name></author><author><name sortKey="Rossignol, E" uniqKey="Rossignol E">E. Rossignol</name></author><author><name sortKey="Fougerou Leurent, C" uniqKey="Fougerou Leurent C">C. Fougerou-Leurent</name></author><author><name sortKey="Dumortier, J" uniqKey="Dumortier J">J. Dumortier</name></author><author><name sortKey="Leroy, V" uniqKey="Leroy V">V. Leroy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Y M" uniqKey="Arabi Y">Y. M. Arabi</name></author><author><name sortKey="Alothman, A" uniqKey="Alothman A">A. Alothman</name></author><author><name sortKey="Balkhy, H H" uniqKey="Balkhy H">H. H. Balkhy</name></author><author><name sortKey="Al Dawood, A" uniqKey="Al Dawood A">A. Al-Dawood</name></author><author><name sortKey="Aljohani, S" uniqKey="Aljohani S">S. Aljohani</name></author><author><name sortKey="Al Harbi, S" uniqKey="Al Harbi S">S. Al Harbi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Y" uniqKey="Arabi Y">Y. Arabi</name></author><author><name sortKey="Balkhy, H" uniqKey="Balkhy H">H. Balkhy</name></author><author><name sortKey="Hajeer, A H" uniqKey="Hajeer A">A. H. Hajeer</name></author><author><name sortKey="Bouchama, A" uniqKey="Bouchama A">A. Bouchama</name></author><author><name sortKey="Hayden, F G" uniqKey="Hayden F">F. G. Hayden</name></author><author><name sortKey="Al Omari, A" uniqKey="Al Omari A">A. Al-Omari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A. Assiri</name></author><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J. A. Al-Tawfiq</name></author><author><name sortKey="Al Rabeeah, A A" uniqKey="Al Rabeeah A">A. A. Al-Rabeeah</name></author><author><name sortKey="Al Rabiah, F A" uniqKey="Al Rabiah F">F. A. Al-Rabiah</name></author><author><name sortKey="Al Hajjar, S" uniqKey="Al Hajjar S">S. Al-Hajjar</name></author><author><name sortKey="Al Barrak, A" uniqKey="Al Barrak A">A. Al-Barrak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Battles, M B" uniqKey="Battles M">M. B. Battles</name></author><author><name sortKey="Langedijk, J P" uniqKey="Langedijk J">J. P. Langedijk</name></author><author><name sortKey="Furmanova Hollenstein, P" uniqKey="Furmanova Hollenstein P">P. Furmanova-Hollenstein</name></author><author><name sortKey="Chaiwatpongsakorn, S" uniqKey="Chaiwatpongsakorn S">S. Chaiwatpongsakorn</name></author><author><name sortKey="Costello, H M" uniqKey="Costello H">H. M. Costello</name></author><author><name sortKey="Kwanten, L" uniqKey="Kwanten L">L. Kwanten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beigel, J H" uniqKey="Beigel J">J. H. Beigel</name></author><author><name sortKey="Voell, J" uniqKey="Voell J">J. Voell</name></author><author><name sortKey="Kumar, P" uniqKey="Kumar P">P. Kumar</name></author><author><name sortKey="Raviprakash, K" uniqKey="Raviprakash K">K. Raviprakash</name></author><author><name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name></author><author><name sortKey="Jiao, J A" uniqKey="Jiao J">J. A. Jiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Belardo, G" uniqKey="Belardo G">G. Belardo</name></author><author><name sortKey="Cenciarelli, O" uniqKey="Cenciarelli O">O. Cenciarelli</name></author><author><name sortKey="La Frazia, S" uniqKey="La Frazia S">S. La Frazia</name></author><author><name sortKey="Rossignol, J F" uniqKey="Rossignol J">J. F. Rossignol</name></author><author><name sortKey="Santoro, M G" uniqKey="Santoro M">M. G. Santoro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Belser, J A" uniqKey="Belser J">J. A. Belser</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author><author><name sortKey="Szretter, K J" uniqKey="Szretter K">K. J. Szretter</name></author><author><name sortKey="Jin, X" uniqKey="Jin X">X. Jin</name></author><author><name sortKey="Aschenbrenner, L M" uniqKey="Aschenbrenner L">L. M. Aschenbrenner</name></author><author><name sortKey="Lee, A" uniqKey="Lee A">A. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bermingham, A" uniqKey="Bermingham A">A. Bermingham</name></author><author><name sortKey="Chand, M A" uniqKey="Chand M">M. A. Chand</name></author><author><name sortKey="Brown, C S" uniqKey="Brown C">C. S. Brown</name></author><author><name sortKey="Aarons, E" uniqKey="Aarons E">E. Aarons</name></author><author><name sortKey="Tong, C" uniqKey="Tong C">C. Tong</name></author><author><name sortKey="Langrish, C" uniqKey="Langrish C">C. Langrish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonavia, A" uniqKey="Bonavia A">A. Bonavia</name></author><author><name sortKey="Franti, M" uniqKey="Franti M">M. Franti</name></author><author><name sortKey="Keaney, E P" uniqKey="Keaney E">E. P. Keaney</name></author><author><name sortKey="Kuhen, K" uniqKey="Kuhen K">K. Kuhen</name></author><author><name sortKey="Seepersaud, M" uniqKey="Seepersaud M">M. Seepersaud</name></author><author><name sortKey="Radetich, B" uniqKey="Radetich B">B. Radetich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonfanti, J F" uniqKey="Bonfanti J">J.-F. Bonfanti</name></author><author><name sortKey="Doublet, F" uniqKey="Doublet F">F. Doublet</name></author><author><name sortKey="Fortin, J" uniqKey="Fortin J">J. Fortin</name></author><author><name sortKey="Lacrampe, J" uniqKey="Lacrampe J">J. Lacrampe</name></author><author><name sortKey="Guillemont, J" uniqKey="Guillemont J">J. Guillemont</name></author><author><name sortKey="Muller, P" uniqKey="Muller P">P. Muller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bonfanti, J F" uniqKey="Bonfanti J">J.-F. Bonfanti</name></author><author><name sortKey="Meyer, C" uniqKey="Meyer C">C. Meyer</name></author><author><name sortKey="Doublet, F" uniqKey="Doublet F">F. Doublet</name></author><author><name sortKey="Fortin, J" uniqKey="Fortin J">J. Fortin</name></author><author><name sortKey="Muller, P" uniqKey="Muller P">P. Muller</name></author><author><name sortKey="Queguiner, L" uniqKey="Queguiner L">L. Queguiner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Borchardt, R A" uniqKey="Borchardt R">R. A. Borchardt</name></author><author><name sortKey="Rolston, K V" uniqKey="Rolston K">K. V. Rolston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boyd, M J" uniqKey="Boyd M">M. J. Boyd</name></author><author><name sortKey="Bandarage, U K" uniqKey="Bandarage U">U. K. Bandarage</name></author><author><name sortKey="Bennett, H" uniqKey="Bennett H">H. Bennett</name></author><author><name sortKey="Byrn, R R" uniqKey="Byrn R">R. R. Byrn</name></author><author><name sortKey="Davies, I" uniqKey="Davies I">I. Davies</name></author><author><name sortKey="Gu, W" uniqKey="Gu W">W. Gu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Byrn, R A" uniqKey="Byrn R">R. A. Byrn</name></author><author><name sortKey="Jones, S M" uniqKey="Jones S">S. M. Jones</name></author><author><name sortKey="Bennett, H B" uniqKey="Bennett H">H. B. Bennett</name></author><author><name sortKey="Bral, C" uniqKey="Bral C">C. Bral</name></author><author><name sortKey="Clark, M P" uniqKey="Clark M">M. P. Clark</name></author><author><name sortKey="Jacobs, M D" uniqKey="Jacobs M">M. D. Jacobs</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Challa, S" uniqKey="Challa S">S. Challa</name></author><author><name sortKey="Scott, A D" uniqKey="Scott A">A. D. Scott</name></author><author><name sortKey="Yuzhakov, O" uniqKey="Yuzhakov O">O. Yuzhakov</name></author><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y. Zhou</name></author><author><name sortKey="Tiong Yip, C L" uniqKey="Tiong Yip C">C. L. Tiong-Yip</name></author><author><name sortKey="Gao, N" uniqKey="Gao N">N. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, S M" uniqKey="Chan S">S. M. Chan</name></author><author><name sortKey="Damdinjav, B" uniqKey="Damdinjav B">B. Damdinjav</name></author><author><name sortKey="Perera, R A" uniqKey="Perera R">R. A. Perera</name></author><author><name sortKey="Chu, D K" uniqKey="Chu D">D. K. Chu</name></author><author><name sortKey="Khishgee, B" uniqKey="Khishgee B">B. Khishgee</name></author><author><name sortKey="Enkhbold, B" uniqKey="Enkhbold B">B. Enkhbold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chapman, J" uniqKey="Chapman J">J. Chapman</name></author><author><name sortKey="Abbott, E" uniqKey="Abbott E">E. Abbott</name></author><author><name sortKey="Alber, D G" uniqKey="Alber D">D. G. Alber</name></author><author><name sortKey="Baxter, R C" uniqKey="Baxter R">R. C. Baxter</name></author><author><name sortKey="Bithell, S K" uniqKey="Bithell S">S. K. Bithell</name></author><author><name sortKey="Henderson, E A" uniqKey="Henderson E">E. A. Henderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaudhuri, S" uniqKey="Chaudhuri S">S. Chaudhuri</name></author><author><name sortKey="Symons, J A" uniqKey="Symons J">J. A. Symons</name></author><author><name sortKey="Deval, J" uniqKey="Deval J">J. Deval</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Clark, M P" uniqKey="Clark M">M. P. Clark</name></author><author><name sortKey="Ledeboer, M W" uniqKey="Ledeboer M">M. W. Ledeboer</name></author><author><name sortKey="Davies, I" uniqKey="Davies I">I. Davies</name></author><author><name sortKey="Byrn, R A" uniqKey="Byrn R">R. A. Byrn</name></author><author><name sortKey="Jones, S M" uniqKey="Jones S">S. M. Jones</name></author><author><name sortKey="Perola, E" uniqKey="Perola E">E. Perola</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Collins, P L" uniqKey="Collins P">P. L. Collins</name></author><author><name sortKey="Fearns, R" uniqKey="Fearns R">R. Fearns</name></author><author><name sortKey="Graham, B S" uniqKey="Graham B">B. S. Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Davidson, S" uniqKey="Davidson S">S. Davidson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, R" uniqKey="Deng R">R. Deng</name></author><author><name sortKey="Lee, A P" uniqKey="Lee A">A. P. Lee</name></author><author><name sortKey="Maia, M" uniqKey="Maia M">M. Maia</name></author><author><name sortKey="Lim, J J" uniqKey="Lim J">J. J. Lim</name></author><author><name sortKey="Burgess, T" uniqKey="Burgess T">T. Burgess</name></author><author><name sortKey="Horn, P" uniqKey="Horn P">P. Horn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Detalle, L" uniqKey="Detalle L">L. Detalle</name></author><author><name sortKey="Larios, A" uniqKey="Larios A">A. Larios</name></author><author><name sortKey="Gallup, L" uniqKey="Gallup L">L. Gallup</name></author><author><name sortKey="Van Geelen, A" uniqKey="Van Geelen A">A. Van Geelen</name></author><author><name sortKey="Duprez, L" uniqKey="Duprez L">L. Duprez</name></author><author><name sortKey="Stohr, T" uniqKey="Stohr T">T. Stohr</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Detalle, L" uniqKey="Detalle L">L. Detalle</name></author><author><name sortKey="Stohr, T" uniqKey="Stohr T">T. Stohr</name></author><author><name sortKey="Palomo, C" uniqKey="Palomo C">C. Palomo</name></author><author><name sortKey="Piedra, P A" uniqKey="Piedra P">P. A. Piedra</name></author><author><name sortKey="Gilbert, B E" uniqKey="Gilbert B">B. E. Gilbert</name></author><author><name sortKey="Mas, V" uniqKey="Mas V">V. Mas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deval, J" uniqKey="Deval J">J. Deval</name></author><author><name sortKey="Hong, J" uniqKey="Hong J">J. Hong</name></author><author><name sortKey="Wang, G" uniqKey="Wang G">G. Wang</name></author><author><name sortKey="Taylor, J" uniqKey="Taylor J">J. Taylor</name></author><author><name sortKey="Smith, L K" uniqKey="Smith L">L. K. Smith</name></author><author><name sortKey="Fung, A" uniqKey="Fung A">A. Fung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Devincenzo, J P" uniqKey="Devincenzo J">J. P. Devincenzo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Devincenzo, J" uniqKey="Devincenzo J">J. Devincenzo</name></author><author><name sortKey="Lambkin Williams, R" uniqKey="Lambkin Williams R">R. Lambkin-Williams</name></author><author><name sortKey="Wilkinson, T" uniqKey="Wilkinson T">T. Wilkinson</name></author><author><name sortKey="Cehelsky, J" uniqKey="Cehelsky J">J. Cehelsky</name></author><author><name sortKey="Nochur, S" uniqKey="Nochur S">S. Nochur</name></author><author><name sortKey="Walsh, E" uniqKey="Walsh E">E. Walsh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Devincenzo, J P" uniqKey="Devincenzo J">J. P. Devincenzo</name></author><author><name sortKey="Mcclure, M W" uniqKey="Mcclure M">M. W. Mcclure</name></author><author><name sortKey="Symons, J A" uniqKey="Symons J">J. A. Symons</name></author><author><name sortKey="Fathi, H" uniqKey="Fathi H">H. Fathi</name></author><author><name sortKey="Westland, C" uniqKey="Westland C">C. Westland</name></author><author><name sortKey="Chanda, S" uniqKey="Chanda S">S. Chanda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Domachowske, J B" uniqKey="Domachowske J">J. B. Domachowske</name></author><author><name sortKey="Khan, A A" uniqKey="Khan A">A. A. Khan</name></author><author><name sortKey="Esser, M T" uniqKey="Esser M">M. T. Esser</name></author><author><name sortKey="Jensen, K" uniqKey="Jensen K">K. Jensen</name></author><author><name sortKey="Takas, T" uniqKey="Takas T">T. Takas</name></author><author><name sortKey="Villafana, T" uniqKey="Villafana T">T. Villafana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dyall, J" uniqKey="Dyall J">J. Dyall</name></author><author><name sortKey="Gross, R" uniqKey="Gross R">R. Gross</name></author><author><name sortKey="Kindrachuk, J" uniqKey="Kindrachuk J">J. Kindrachuk</name></author><author><name sortKey="Johnson, R F" uniqKey="Johnson R">R. F. Johnson</name></author><author><name sortKey="Olinger, G G" uniqKey="Olinger G">G. G. Olinger</name></author><author><name sortKey="Hensley, L E" uniqKey="Hensley L">L. E. Hensley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ekiert, D C" uniqKey="Ekiert D">D. C. Ekiert</name></author><author><name sortKey="Friesen, R H" uniqKey="Friesen R">R. H. Friesen</name></author><author><name sortKey="Bhabha, G" uniqKey="Bhabha G">G. Bhabha</name></author><author><name sortKey="Kwaks, T" uniqKey="Kwaks T">T. Kwaks</name></author><author><name sortKey="Jongeneelen, M" uniqKey="Jongeneelen M">M. Jongeneelen</name></author><author><name sortKey="Yu, W" uniqKey="Yu W">W. Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Enjuanes, L" uniqKey="Enjuanes L">L. Enjuanes</name></author><author><name sortKey="Zuniga, S" uniqKey="Zuniga S">S. Zuniga</name></author><author><name sortKey="Castano Rodriguez, C" uniqKey="Castano Rodriguez C">C. Castano-Rodriguez</name></author><author><name sortKey="Gutierrez Alvarez, J" uniqKey="Gutierrez Alvarez J">J. Gutierrez-Alvarez</name></author><author><name sortKey="Canton, J" uniqKey="Canton J">J. Canton</name></author><author><name sortKey="Sola, I" uniqKey="Sola I">I. Sola</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Erbelding, E J" uniqKey="Erbelding E">E. J. Erbelding</name></author><author><name sortKey="Post, D J" uniqKey="Post D">D. J. Post</name></author><author><name sortKey="Stemmy, E J" uniqKey="Stemmy E">E. J. Stemmy</name></author><author><name sortKey="Roberts, P C" uniqKey="Roberts P">P. C. Roberts</name></author><author><name sortKey="Augustine, A D" uniqKey="Augustine A">A. D. Augustine</name></author><author><name sortKey="Ferguson, S" uniqKey="Ferguson S">S. Ferguson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. De Wit</name></author><author><name sortKey="Rasmussen, A L" uniqKey="Rasmussen A">A. L. Rasmussen</name></author><author><name sortKey="Feldmann, F" uniqKey="Feldmann F">F. Feldmann</name></author><author><name sortKey="Okumura, A" uniqKey="Okumura A">A. Okumura</name></author><author><name sortKey="Scott, D P" uniqKey="Scott D">D. P. Scott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferkol, T" uniqKey="Ferkol T">T. Ferkol</name></author><author><name sortKey="Schraufnagel, D" uniqKey="Schraufnagel D">D. Schraufnagel</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Friesen, R H" uniqKey="Friesen R">R. H. Friesen</name></author><author><name sortKey="Koudstaal, W" uniqKey="Koudstaal W">W. Koudstaal</name></author><author><name sortKey="Koldijk, M H" uniqKey="Koldijk M">M. H. Koldijk</name></author><author><name sortKey="Weverling, G J" uniqKey="Weverling G">G. J. Weverling</name></author><author><name sortKey="Brakenhoff, J P" uniqKey="Brakenhoff J">J. P. Brakenhoff</name></author><author><name sortKey="Lenting, P J" uniqKey="Lenting P">P. J. Lenting</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frogel, M" uniqKey="Frogel M">M. Frogel</name></author><author><name sortKey="Nerwen, C" uniqKey="Nerwen C">C. Nerwen</name></author><author><name sortKey="Cohen, A" uniqKey="Cohen A">A. Cohen</name></author><author><name sortKey="Vanveldhuisen, P" uniqKey="Vanveldhuisen P">P. Vanveldhuisen</name></author><author><name sortKey="Harrington, M" uniqKey="Harrington M">M. Harrington</name></author><author><name sortKey="Boron, M" uniqKey="Boron M">M. Boron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fukao, K" uniqKey="Fukao K">K. Fukao</name></author><author><name sortKey="Noshi, T" uniqKey="Noshi T">T. Noshi</name></author><author><name sortKey="Yamamoto, A" uniqKey="Yamamoto A">A. Yamamoto</name></author><author><name sortKey="Kitano, M" uniqKey="Kitano M">M. Kitano</name></author><author><name sortKey="Ando, Y" uniqKey="Ando Y">Y. Ando</name></author><author><name sortKey="Noda, T" uniqKey="Noda T">T. Noda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Furuta, Y" uniqKey="Furuta Y">Y. Furuta</name></author><author><name sortKey="Komeno, T" uniqKey="Komeno T">T. Komeno</name></author><author><name sortKey="Nakamura, T" uniqKey="Nakamura T">T. Nakamura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Furuta, Y" uniqKey="Furuta Y">Y. Furuta</name></author><author><name sortKey="Takahashi, K" uniqKey="Takahashi K">K. Takahashi</name></author><author><name sortKey="Kuno Maekawa, M" uniqKey="Kuno Maekawa M">M. Kuno-Maekawa</name></author><author><name sortKey="Sangawa, H" uniqKey="Sangawa H">H. Sangawa</name></author><author><name sortKey="Uehara, S" uniqKey="Uehara S">S. Uehara</name></author><author><name sortKey="Kozaki, K" uniqKey="Kozaki K">K. Kozaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gottlieb, J" uniqKey="Gottlieb J">J. Gottlieb</name></author><author><name sortKey="Zamora, M R" uniqKey="Zamora M">M. R. Zamora</name></author><author><name sortKey="Hodges, T" uniqKey="Hodges T">T. Hodges</name></author><author><name sortKey="Musk, A" uniqKey="Musk A">A. Musk</name></author><author><name sortKey="Sommerwerk, U" uniqKey="Sommerwerk U">U. Sommerwerk</name></author><author><name sortKey="Dilling, D" uniqKey="Dilling D">D. Dilling</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Griffin, M P" uniqKey="Griffin M">M. P. Griffin</name></author><author><name sortKey="Khan, A A" uniqKey="Khan A">A. A. Khan</name></author><author><name sortKey="Esser, M T" uniqKey="Esser M">M. T. Esser</name></author><author><name sortKey="Jensen, K" uniqKey="Jensen K">K. Jensen</name></author><author><name sortKey="Takas, T" uniqKey="Takas T">T. Takas</name></author><author><name sortKey="Kankam, M K" uniqKey="Kankam M">M. K. Kankam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Griffiths, C" uniqKey="Griffiths C">C. Griffiths</name></author><author><name sortKey="Drews, S J" uniqKey="Drews S">S. J. Drews</name></author><author><name sortKey="Marchant, D J" uniqKey="Marchant D">D. J. Marchant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gurnett Bander, A" uniqKey="Gurnett Bander A">A. Gurnett-Bander</name></author><author><name sortKey="Perez Caballero, D" uniqKey="Perez Caballero D">D. Perez-Caballero</name></author><author><name sortKey="Sivapalasingam, S" uniqKey="Sivapalasingam S">S. Sivapalasingam</name></author><author><name sortKey="Duan, X" uniqKey="Duan X">X. Duan</name></author><author><name sortKey="Macdonald, D" uniqKey="Macdonald D">D. Macdonald</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haffizulla, J" uniqKey="Haffizulla J">J. Haffizulla</name></author><author><name sortKey="Hartman, A" uniqKey="Hartman A">A. Hartman</name></author><author><name sortKey="Hoppers, M" uniqKey="Hoppers M">M. Hoppers</name></author><author><name sortKey="Resnick, H" uniqKey="Resnick H">H. Resnick</name></author><author><name sortKey="Samudrala, S" uniqKey="Samudrala S">S. Samudrala</name></author><author><name sortKey="Ginocchio, C" uniqKey="Ginocchio C">C. Ginocchio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hanfelt Goade, D" uniqKey="Hanfelt Goade D">D. Hanfelt-Goade</name></author><author><name sortKey="Maimon, N" uniqKey="Maimon N">N. Maimon</name></author><author><name sortKey="Nimer, A" uniqKey="Nimer A">A. Nimer</name></author><author><name sortKey="Riviere, F" uniqKey="Riviere F">F. Riviere</name></author><author><name sortKey="Catherinot, E" uniqKey="Catherinot E">E. Catherinot</name></author><author><name sortKey="Ison, M" uniqKey="Ison M">M. Ison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hanton, G" uniqKey="Hanton G">G. Hanton</name></author><author><name sortKey="Detalle, L" uniqKey="Detalle L">L. Detalle</name></author><author><name sortKey="Priem, S" uniqKey="Priem S">S. Priem</name></author><author><name sortKey="Bouche, M P" uniqKey="Bouche M">M.-P. Bouche</name></author><author><name sortKey="Depla, E" uniqKey="Depla E">E. Depla</name></author><author><name sortKey="Baumeister, J" uniqKey="Baumeister J">J. Baumeister</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hayden, F G" uniqKey="Hayden F">F. G. Hayden</name></author><author><name sortKey="Sugaya, N" uniqKey="Sugaya N">N. Sugaya</name></author><author><name sortKey="Hirotsu, N" uniqKey="Hirotsu N">N. Hirotsu</name></author><author><name sortKey="Lee, N" uniqKey="Lee N">N. Lee</name></author><author><name sortKey="De Jong, M D" uniqKey="De Jong M">M. D. De Jong</name></author><author><name sortKey="Hurt, A C" uniqKey="Hurt A">A. C. Hurt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haynes, L M" uniqKey="Haynes L">L. M. Haynes</name></author><author><name sortKey="Caidi, H" uniqKey="Caidi H">H. Caidi</name></author><author><name sortKey="Radu, G U" uniqKey="Radu G">G. U. Radu</name></author><author><name sortKey="Miao, C" uniqKey="Miao C">C. Miao</name></author><author><name sortKey="Harcourt, J L" uniqKey="Harcourt J">J. L. Harcourt</name></author><author><name sortKey="Tripp, R A" uniqKey="Tripp R">R. A. Tripp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heylen, E" uniqKey="Heylen E">E. Heylen</name></author><author><name sortKey="Neyts, J" uniqKey="Neyts J">J. Neyts</name></author><author><name sortKey="Jochmans, D" uniqKey="Jochmans D">D. Jochmans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hotard, A L" uniqKey="Hotard A">A. L. Hotard</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S. Lee</name></author><author><name sortKey="Currier, M G" uniqKey="Currier M">M. G. Currier</name></author><author><name sortKey="Crowe, J E" uniqKey="Crowe J">J. E. Crowe</name></author><author><name sortKey="Sakamoto, K" uniqKey="Sakamoto K">K. Sakamoto</name></author><author><name sortKey="Newcomb, D C" uniqKey="Newcomb D">D. C. Newcomb</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huntjens, D R" uniqKey="Huntjens D">D. R. Huntjens</name></author><author><name sortKey="Ouwerkerk Mahadevan, S" uniqKey="Ouwerkerk Mahadevan S">S. Ouwerkerk-Mahadevan</name></author><author><name sortKey="Brochot, A" uniqKey="Brochot A">A. Brochot</name></author><author><name sortKey="Rusch, S" uniqKey="Rusch S">S. Rusch</name></author><author><name sortKey="Stevens, M" uniqKey="Stevens M">M. Stevens</name></author><author><name sortKey="Verloes, R" uniqKey="Verloes R">R. Verloes</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Ison, M G" uniqKey="Ison M">M. G. Ison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ispas, G" uniqKey="Ispas G">G. Ispas</name></author><author><name sortKey="Koul, A" uniqKey="Koul A">A. Koul</name></author><author><name sortKey="Verbeeck, J" uniqKey="Verbeeck J">J. Verbeeck</name></author><author><name sortKey="Sheehan, J" uniqKey="Sheehan J">J. Sheehan</name></author><author><name sortKey="Sanders Beer, B" uniqKey="Sanders Beer B">B. Sanders-Beer</name></author><author><name sortKey="Roymans, D" uniqKey="Roymans D">D. Roymans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Israel, S" uniqKey="Israel S">S. Israel</name></author><author><name sortKey="Rusch, S" uniqKey="Rusch S">S. Rusch</name></author><author><name sortKey="Devincenzo, J" uniqKey="Devincenzo J">J. Devincenzo</name></author><author><name sortKey="Boyers, A" uniqKey="Boyers A">A. Boyers</name></author><author><name sortKey="Fok Seang, J" uniqKey="Fok Seang J">J. Fok-Seang</name></author><author><name sortKey="Huntjens, D" uniqKey="Huntjens D">D. Huntjens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jin, Y" uniqKey="Jin Y">Y. Jin</name></author><author><name sortKey="Lei, C" uniqKey="Lei C">C. Lei</name></author><author><name sortKey="Hu, D" uniqKey="Hu D">D. Hu</name></author><author><name sortKey="Dimitrov, D S" uniqKey="Dimitrov D">D. S. Dimitrov</name></author><author><name sortKey="Ying, T" uniqKey="Ying T">T. Ying</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, S M" uniqKey="Johnson S">S. M. Johnson</name></author><author><name sortKey="Mcnally, B A" uniqKey="Mcnally B">B. A. McNally</name></author><author><name sortKey="Ioannidis, I" uniqKey="Ioannidis I">I. Ioannidis</name></author><author><name sortKey="Flano, E" uniqKey="Flano E">E. Flano</name></author><author><name sortKey="Teng, M N" uniqKey="Teng M">M. N. Teng</name></author><author><name sortKey="Oomens, A G" uniqKey="Oomens A">A. G. Oomens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, J C" uniqKey="Jones J">J. C. Jones</name></author><author><name sortKey="Kumar, G" uniqKey="Kumar G">G. Kumar</name></author><author><name sortKey="Barman, S" uniqKey="Barman S">S. Barman</name></author><author><name sortKey="Najera, I" uniqKey="Najera I">I. Najera</name></author><author><name sortKey="White, S W" uniqKey="White S">S. W. White</name></author><author><name sortKey="Webby, R J" uniqKey="Webby R">R. J. Webby</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jordan, P C" uniqKey="Jordan P">P. C. Jordan</name></author><author><name sortKey="Stevens, S K" uniqKey="Stevens S">S. K. Stevens</name></author><author><name sortKey="Deval, J" uniqKey="Deval J">J. Deval</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jorquera, P A" uniqKey="Jorquera P">P. A. Jorquera</name></author><author><name sortKey="Tripp, R A" uniqKey="Tripp R">R. A. Tripp</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kallewaard, N L" uniqKey="Kallewaard N">N. L. Kallewaard</name></author><author><name sortKey="Corti, D" uniqKey="Corti D">D. Corti</name></author><author><name sortKey="Collins, P J" uniqKey="Collins P">P. J. Collins</name></author><author><name sortKey="Neu, U" uniqKey="Neu U">U. Neu</name></author><author><name sortKey="Mcauliffe, J M" uniqKey="Mcauliffe J">J. M. McAuliffe</name></author><author><name sortKey="Benjamin, E" uniqKey="Benjamin E">E. Benjamin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kapoor, M" uniqKey="Kapoor M">M. Kapoor</name></author><author><name sortKey="Pringle, K" uniqKey="Pringle K">K. Pringle</name></author><author><name sortKey="Kumar, A" uniqKey="Kumar A">A. Kumar</name></author><author><name sortKey="Dearth, S" uniqKey="Dearth S">S. Dearth</name></author><author><name sortKey="Liu, L" uniqKey="Liu L">L. Liu</name></author><author><name sortKey="Lovchik, J" uniqKey="Lovchik J">J. Lovchik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khalid, M" uniqKey="Khalid M">M. Khalid</name></author><author><name sortKey="Al Rabiah, F" uniqKey="Al Rabiah F">F. Al Rabiah</name></author><author><name sortKey="Khan, B" uniqKey="Khan B">B. Khan</name></author><author><name sortKey="Al Mobeireek, A" uniqKey="Al Mobeireek A">A. Al Mobeireek</name></author><author><name sortKey="Butt, T S" uniqKey="Butt T">T. S. Butt</name></author><author><name sortKey="Al Mutairy, E" uniqKey="Al Mutairy E">E. Al Mutairy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ki, M" uniqKey="Ki M">M. Ki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y I" uniqKey="Kim Y">Y. I. Kim</name></author><author><name sortKey="Pareek, R" uniqKey="Pareek R">R. Pareek</name></author><author><name sortKey="Murphy, R" uniqKey="Murphy R">R. Murphy</name></author><author><name sortKey="Harrison, L" uniqKey="Harrison L">L. Harrison</name></author><author><name sortKey="Farrell, E" uniqKey="Farrell E">E. Farrell</name></author><author><name sortKey="Cook, R" uniqKey="Cook R">R. Cook</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, J" uniqKey="Kim J">J. Kim</name></author><author><name sortKey="Seong, R K" uniqKey="Seong R">R.-K. Seong</name></author><author><name sortKey="Kumar, M" uniqKey="Kumar M">M. Kumar</name></author><author><name sortKey="Shin, O S" uniqKey="Shin O">O. S. Shin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, U J" uniqKey="Kim U">U. J. Kim</name></author><author><name sortKey="Won, E J" uniqKey="Won E">E. J. Won</name></author><author><name sortKey="Kee, S J" uniqKey="Kee S">S. J. Kee</name></author><author><name sortKey="Jung, S I" uniqKey="Jung S">S. I. Jung</name></author><author><name sortKey="Jang, H C" uniqKey="Jang H">H. C. Jang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koszalka, P" uniqKey="Koszalka P">P. Koszalka</name></author><author><name sortKey="Tilmanis, D" uniqKey="Tilmanis D">D. Tilmanis</name></author><author><name sortKey="Hurt, A C" uniqKey="Hurt A">A. C. Hurt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koudstaal, W" uniqKey="Koudstaal W">W. Koudstaal</name></author><author><name sortKey="Koldijk, M H" uniqKey="Koldijk M">M. H. Koldijk</name></author><author><name sortKey="Brakenhoff, J P" uniqKey="Brakenhoff J">J. P. Brakenhoff</name></author><author><name sortKey="Cornelissen, L A" uniqKey="Cornelissen L">L. A. Cornelissen</name></author><author><name sortKey="Weverling, G J" uniqKey="Weverling G">G. J. Weverling</name></author><author><name sortKey="Friesen, R H" uniqKey="Friesen R">R. H. Friesen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lim, J J" uniqKey="Lim J">J. J. Lim</name></author><author><name sortKey="Deng, R" uniqKey="Deng R">R. Deng</name></author><author><name sortKey="Derby, M A" uniqKey="Derby M">M. A. Derby</name></author><author><name sortKey="Larouche, R" uniqKey="Larouche R">R. Larouche</name></author><author><name sortKey="Horn, P" uniqKey="Horn P">P. Horn</name></author><author><name sortKey="Anderson, M" uniqKey="Anderson M">M. Anderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, P Y" uniqKey="Lu P">P. Y. Lu</name></author><author><name sortKey="Evans, D M" uniqKey="Evans D">D. M. Evans</name></author><author><name sortKey="Xu, J J" uniqKey="Xu J">J. J. Xu</name></author><author><name sortKey="Lu, A Y" uniqKey="Lu A">A. Y. Lu</name></author><author><name sortKey="Ge, Q" uniqKey="Ge Q">Q. Ge</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luke, T" uniqKey="Luke T">T. Luke</name></author><author><name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Channappanavar, R" uniqKey="Channappanavar R">R. Channappanavar</name></author><author><name sortKey="Coleman, C M" uniqKey="Coleman C">C. M. Coleman</name></author><author><name sortKey="Jiao, J A" uniqKey="Jiao J">J. A. Jiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mackman, R L" uniqKey="Mackman R">R. L. Mackman</name></author><author><name sortKey="Sangi, M" uniqKey="Sangi M">M. Sangi</name></author><author><name sortKey="Sperandio, D" uniqKey="Sperandio D">D. Sperandio</name></author><author><name sortKey="Parrish, J P" uniqKey="Parrish J">J. P. Parrish</name></author><author><name sortKey="Eisenberg, E" uniqKey="Eisenberg E">E. Eisenberg</name></author><author><name sortKey="Perron, M" uniqKey="Perron M">M. Perron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mair Jenkins, J" uniqKey="Mair Jenkins J">J. Mair-Jenkins</name></author><author><name sortKey="Saavedra Campos, M" uniqKey="Saavedra Campos M">M. Saavedra-Campos</name></author><author><name sortKey="Baillie, J K" uniqKey="Baillie J">J. K. Baillie</name></author><author><name sortKey="Cleary, P" uniqKey="Cleary P">P. Cleary</name></author><author><name sortKey="Khaw, F M" uniqKey="Khaw F">F. M. Khaw</name></author><author><name sortKey="Lim, W S" uniqKey="Lim W">W. S. Lim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malakhov, M P" uniqKey="Malakhov M">M. P. Malakhov</name></author><author><name sortKey="Aschenbrenner, L M" uniqKey="Aschenbrenner L">L. M. Aschenbrenner</name></author><author><name sortKey="Smee, D F" uniqKey="Smee D">D. F. Smee</name></author><author><name sortKey="Wandersee, M K" uniqKey="Wandersee M">M. K. Wandersee</name></author><author><name sortKey="Sidwell, R W" uniqKey="Sidwell R">R. W. Sidwell</name></author><author><name sortKey="Gubareva, L V" uniqKey="Gubareva L">L. V. Gubareva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marjuki, H" uniqKey="Marjuki H">H. Marjuki</name></author><author><name sortKey="Mishin, V P" uniqKey="Mishin V">V. P. Mishin</name></author><author><name sortKey="Chesnokov, A P" uniqKey="Chesnokov A">A. P. Chesnokov</name></author><author><name sortKey="De La Cruz, J A" uniqKey="De La Cruz J">J. A. De La Cruz</name></author><author><name sortKey="Fry, A M" uniqKey="Fry A">A. M. Fry</name></author><author><name sortKey="Villanueva, J" uniqKey="Villanueva J">J. Villanueva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marjuki, H" uniqKey="Marjuki H">H. Marjuki</name></author><author><name sortKey="Mishin, V P" uniqKey="Mishin V">V. P. Mishin</name></author><author><name sortKey="Chesnokov, A P" uniqKey="Chesnokov A">A. P. Chesnokov</name></author><author><name sortKey="Jones, J" uniqKey="Jones J">J. Jones</name></author><author><name sortKey="De La Cruz, J A" uniqKey="De La Cruz J">J. A. De La Cruz</name></author><author><name sortKey="Sleeman, K" uniqKey="Sleeman K">K. Sleeman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marty, F" uniqKey="Marty F">F. Marty</name></author><author><name sortKey="Chemaly, R" uniqKey="Chemaly R">R. Chemaly</name></author><author><name sortKey="Liakopoulou, E" uniqKey="Liakopoulou E">E. Liakopoulou</name></author><author><name sortKey="Dent, J" uniqKey="Dent J">J. Dent</name></author><author><name sortKey="Powell, K" uniqKey="Powell K">K. Powell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsushita, H" uniqKey="Matsushita H">H. Matsushita</name></author><author><name sortKey="Sano, A" uniqKey="Sano A">A. Sano</name></author><author><name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name></author><author><name sortKey="Jiao, J A" uniqKey="Jiao J">J. A. Jiao</name></author><author><name sortKey="Kasinathan, P" uniqKey="Kasinathan P">P. Kasinathan</name></author><author><name sortKey="Sullivan, E J" uniqKey="Sullivan E">E. J. Sullivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcbride, J M" uniqKey="Mcbride J">J. M. McBride</name></author><author><name sortKey="Lim, J J" uniqKey="Lim J">J. J. Lim</name></author><author><name sortKey="Burgess, T" uniqKey="Burgess T">T. Burgess</name></author><author><name sortKey="Deng, R" uniqKey="Deng R">R. Deng</name></author><author><name sortKey="Derby, M A" uniqKey="Derby M">M. A. Derby</name></author><author><name sortKey="Maia, M" uniqKey="Maia M">M. Maia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcintosh, K" uniqKey="Mcintosh K">K. McIntosh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z. A. Memish</name></author><author><name sortKey="Zumla, A I" uniqKey="Zumla A">A. I. Zumla</name></author><author><name sortKey="Assiri, A" uniqKey="Assiri A">A. Assiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mo, Y" uniqKey="Mo Y">Y. Mo</name></author><author><name sortKey="Fisher, D" uniqKey="Fisher D">D. Fisher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Modjarrad, K" uniqKey="Modjarrad K">K. Modjarrad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Momattin, H" uniqKey="Momattin H">H. Momattin</name></author><author><name sortKey="Mohammed, K" uniqKey="Mohammed K">K. Mohammed</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z. A. Memish</name></author><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J. A. Al-Tawfiq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Morris, J" uniqKey="Morris J">J. Morris</name></author><author><name sortKey="Blount, R" uniqKey="Blount R">R. Blount</name></author><author><name sortKey="Savage, R" uniqKey="Savage R">R. Savage</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moss, R B" uniqKey="Moss R">R. B. Moss</name></author><author><name sortKey="Hansen, C" uniqKey="Hansen C">C. Hansen</name></author><author><name sortKey="Sanders, R L" uniqKey="Sanders R">R. L. Sanders</name></author><author><name sortKey="Hawley, S" uniqKey="Hawley S">S. Hawley</name></author><author><name sortKey="Li, T" uniqKey="Li T">T. Li</name></author><author><name sortKey="Steigbigel, R T" uniqKey="Steigbigel R">R. T. Steigbigel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mustafa, S" uniqKey="Mustafa S">S. Mustafa</name></author><author><name sortKey="Balkhy, H" uniqKey="Balkhy H">H. Balkhy</name></author><author><name sortKey="Gabere, M N" uniqKey="Gabere M">M. N. Gabere</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nakamura, G" uniqKey="Nakamura G">G. Nakamura</name></author><author><name sortKey="Chai, N" uniqKey="Chai N">N. Chai</name></author><author><name sortKey="Park, S" uniqKey="Park S">S. Park</name></author><author><name sortKey="Chiang, N" uniqKey="Chiang N">N. Chiang</name></author><author><name sortKey="Lin, Z" uniqKey="Lin Z">Z. Lin</name></author><author><name sortKey="Chiu, H" uniqKey="Chiu H">H. Chiu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Noshi, T" uniqKey="Noshi T">T. Noshi</name></author><author><name sortKey="Kitano, M" uniqKey="Kitano M">M. Kitano</name></author><author><name sortKey="Taniguchi, K" uniqKey="Taniguchi K">K. Taniguchi</name></author><author><name sortKey="Yamamoto, A" uniqKey="Yamamoto A">A. Yamamoto</name></author><author><name sortKey="Omoto, S" uniqKey="Omoto S">S. Omoto</name></author><author><name sortKey="Baba, K" uniqKey="Baba K">K. Baba</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="O Rien, K L" uniqKey="O Rien K">K. L. O’brien</name></author><author><name sortKey="Chandran, A" uniqKey="Chandran A">A. Chandran</name></author><author><name sortKey="Weatherholtz, R" uniqKey="Weatherholtz R">R. Weatherholtz</name></author><author><name sortKey="Jafri, H S" uniqKey="Jafri H">H. S. Jafri</name></author><author><name sortKey="Griffin, M P" uniqKey="Griffin M">M. P. Griffin</name></author><author><name sortKey="Bellamy, T" uniqKey="Bellamy T">T. Bellamy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Omrani, A S" uniqKey="Omrani A">A. S. Omrani</name></author><author><name sortKey="Shalhoub, S" uniqKey="Shalhoub S">S. Shalhoub</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ormond, L" uniqKey="Ormond L">L. Ormond</name></author><author><name sortKey="Liu, P" uniqKey="Liu P">P. Liu</name></author><author><name sortKey="Matuszewski, S" uniqKey="Matuszewski S">S. Matuszewski</name></author><author><name sortKey="Renzette, N" uniqKey="Renzette N">N. Renzette</name></author><author><name sortKey="Bank, C" uniqKey="Bank C">C. Bank</name></author><author><name sortKey="Zeldovich, K" uniqKey="Zeldovich K">K. Zeldovich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paden, C R" uniqKey="Paden C">C. R. Paden</name></author><author><name sortKey="Yusof, M" uniqKey="Yusof M">M. Yusof</name></author><author><name sortKey="Al Hammadi, Z M" uniqKey="Al Hammadi Z">Z. M. Al Hammadi</name></author><author><name sortKey="Queen, K" uniqKey="Queen K">K. Queen</name></author><author><name sortKey="Tao, Y" uniqKey="Tao Y">Y. Tao</name></author><author><name sortKey="Eltahir, Y M" uniqKey="Eltahir Y">Y. M. Eltahir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Palese, P" uniqKey="Palese P">P. Palese</name></author><author><name sortKey="Bodo, G" uniqKey="Bodo G">G. Bodo</name></author><author><name sortKey="Tuppy, H" uniqKey="Tuppy H">H. Tuppy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, S Y" uniqKey="Park S">S. Y. Park</name></author><author><name sortKey="Lee, J S" uniqKey="Lee J">J. S. Lee</name></author><author><name sortKey="Son, J S" uniqKey="Son J">J. S. Son</name></author><author><name sortKey="Ko, J H" uniqKey="Ko J">J. H. Ko</name></author><author><name sortKey="Peck, K R" uniqKey="Peck K">K. R. Peck</name></author><author><name sortKey="Jung, Y" uniqKey="Jung Y">Y. Jung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pascal, K E" uniqKey="Pascal K">K. E. Pascal</name></author><author><name sortKey="Coleman, C M" uniqKey="Coleman C">C. M. Coleman</name></author><author><name sortKey="Mujica, A O" uniqKey="Mujica A">A. O. Mujica</name></author><author><name sortKey="Kamat, V" uniqKey="Kamat V">V. Kamat</name></author><author><name sortKey="Badithe, A" uniqKey="Badithe A">A. Badithe</name></author><author><name sortKey="Fairhurst, J" uniqKey="Fairhurst J">J. Fairhurst</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paules, C I" uniqKey="Paules C">C. I. Paules</name></author><author><name sortKey="Lakdawala, S" uniqKey="Lakdawala S">S. Lakdawala</name></author><author><name sortKey="Mcauliffe, J M" uniqKey="Mcauliffe J">J. M. McAuliffe</name></author><author><name sortKey="Paskel, M" uniqKey="Paskel M">M. Paskel</name></author><author><name sortKey="Vogel, L" uniqKey="Vogel L">L. Vogel</name></author><author><name sortKey="Kallewaard, N L" uniqKey="Kallewaard N">N. L. Kallewaard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Petersen, E" uniqKey="Petersen E">E. Petersen</name></author><author><name sortKey="Hui, D S" uniqKey="Hui D">D. S. Hui</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pielak, R M" uniqKey="Pielak R">R. M. Pielak</name></author><author><name sortKey="Chou, J J" uniqKey="Chou J">J. J. Chou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Putri, W" uniqKey="Putri W">W. Putri</name></author><author><name sortKey="Muscatello, D J" uniqKey="Muscatello D">D. J. Muscatello</name></author><author><name sortKey="Stockwell, M S" uniqKey="Stockwell M">M. S. Stockwell</name></author><author><name sortKey="Newall, A T" uniqKey="Newall A">A. T. Newall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rabaan, A A" uniqKey="Rabaan A">A. A. Rabaan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rabaan, A A" uniqKey="Rabaan A">A. A. Rabaan</name></author><author><name sortKey="Alahmed, S H" uniqKey="Alahmed S">S. H. Alahmed</name></author><author><name sortKey="Bazzi, A M" uniqKey="Bazzi A">A. M. Bazzi</name></author><author><name sortKey="Alhani, H M" uniqKey="Alhani H">H. M. Alhani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rossignol, J F" uniqKey="Rossignol J">J. F. Rossignol</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rossignol, J F" uniqKey="Rossignol J">J. F. Rossignol</name></author><author><name sortKey="La Frazia, S" uniqKey="La Frazia S">S. La Frazia</name></author><author><name sortKey="Chiappa, L" uniqKey="Chiappa L">L. Chiappa</name></author><author><name sortKey="Ciucci, A" uniqKey="Ciucci A">A. Ciucci</name></author><author><name sortKey="Santoro, M G" uniqKey="Santoro M">M. G. Santoro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rouan, M C" uniqKey="Rouan M">M.-C. Rouan</name></author><author><name sortKey="Gevers, T" uniqKey="Gevers T">T. Gevers</name></author><author><name sortKey="Roymans, D" uniqKey="Roymans D">D. Roymans</name></author><author><name sortKey="De Zwart, L" uniqKey="De Zwart L">L. De Zwart</name></author><author><name sortKey="Nauwelaers, D" uniqKey="Nauwelaers D">D. Nauwelaers</name></author><author><name sortKey="De Meulder, M" uniqKey="De Meulder M">M. De Meulder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roymans, D" uniqKey="Roymans D">D. Roymans</name></author><author><name sortKey="Rigaux, P" uniqKey="Rigaux P">P. Rigaux</name></author><author><name sortKey="Kwanten, L" uniqKey="Kwanten L">L. Kwanten</name></author><author><name sortKey="Vandesteene, C" uniqKey="Vandesteene C">C. Vandesteene</name></author><author><name sortKey="Van Ginderen, M" uniqKey="Van Ginderen M">M. Van Ginderen</name></author><author><name sortKey="Van Den Berg, J" uniqKey="Van Den Berg J">J. Van Den Berg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Samuel, D" uniqKey="Samuel D">D. Samuel</name></author><author><name sortKey="Xing, W" uniqKey="Xing W">W. Xing</name></author><author><name sortKey="Niedziela Majka, A" uniqKey="Niedziela Majka A">A. Niedziela-Majka</name></author><author><name sortKey="Wong, J S" uniqKey="Wong J">J. S. Wong</name></author><author><name sortKey="Hung, M" uniqKey="Hung M">M. Hung</name></author><author><name sortKey="Brendza, K M" uniqKey="Brendza K">K. M. Brendza</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schickli, J H" uniqKey="Schickli J">J. H. Schickli</name></author><author><name sortKey="Whitacre, D C" uniqKey="Whitacre D">D. C. Whitacre</name></author><author><name sortKey="Tang, R S" uniqKey="Tang R">R. S. Tang</name></author><author><name sortKey="Kaur, J" uniqKey="Kaur J">J. Kaur</name></author><author><name sortKey="Lawlor, H" uniqKey="Lawlor H">H. Lawlor</name></author><author><name sortKey="Peters, C J" uniqKey="Peters C">C. J. Peters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schnell, J R" uniqKey="Schnell J">J. R. Schnell</name></author><author><name sortKey="Chou, J J" uniqKey="Chou J">J. J. Chou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shahabi, A" uniqKey="Shahabi A">A. Shahabi</name></author><author><name sortKey="Peneva, D" uniqKey="Peneva D">D. Peneva</name></author><author><name sortKey="Incerti, D" uniqKey="Incerti D">D. Incerti</name></author><author><name sortKey="Mclaurin, K" uniqKey="Mclaurin K">K. McLaurin</name></author><author><name sortKey="Stevens, W" uniqKey="Stevens W">W. Stevens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shalhoub, S" uniqKey="Shalhoub S">S. Shalhoub</name></author><author><name sortKey="Farahat, F" uniqKey="Farahat F">F. Farahat</name></author><author><name sortKey="Al Jiffri, A" uniqKey="Al Jiffri A">A. Al-Jiffri</name></author><author><name sortKey="Simhairi, R" uniqKey="Simhairi R">R. Simhairi</name></author><author><name sortKey="Shamma, O" uniqKey="Shamma O">O. Shamma</name></author><author><name sortKey="Siddiqi, N" uniqKey="Siddiqi N">N. Siddiqi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shaw, M L" uniqKey="Shaw M">M. L. Shaw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sidwell, R W" uniqKey="Sidwell R">R. W. Sidwell</name></author><author><name sortKey="Barnard, D L" uniqKey="Barnard D">D. L. Barnard</name></author><author><name sortKey="Day, C W" uniqKey="Day C">C. W. Day</name></author><author><name sortKey="Smee, D F" uniqKey="Smee D">D. F. Smee</name></author><author><name sortKey="Bailey, K W" uniqKey="Bailey K">K. W. Bailey</name></author><author><name sortKey="Wong, M H" uniqKey="Wong M">M. H. Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sivapalasingam, S" uniqKey="Sivapalasingam S">S. Sivapalasingam</name></author><author><name sortKey="Caballero Perez, D" uniqKey="Caballero Perez D">D. Caballero-Perez</name></author><author><name sortKey="Houghton, M" uniqKey="Houghton M">M. Houghton</name></author><author><name sortKey="Yang, F" uniqKey="Yang F">F. Yang</name></author><author><name sortKey="Davis, J" uniqKey="Davis J">J. Davis</name></author><author><name sortKey="Gao, B" uniqKey="Gao B">B. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sleeman, K" uniqKey="Sleeman K">K. Sleeman</name></author><author><name sortKey="Mishin, V P" uniqKey="Mishin V">V. P. Mishin</name></author><author><name sortKey="Guo, Z" uniqKey="Guo Z">Z. Guo</name></author><author><name sortKey="Garten, R J" uniqKey="Garten R">R. J. Garten</name></author><author><name sortKey="Balish, A" uniqKey="Balish A">A. Balish</name></author><author><name sortKey="Fry, A M" uniqKey="Fry A">A. M. Fry</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smee, D F" uniqKey="Smee D">D. F. Smee</name></author><author><name sortKey="Barnard, D L" uniqKey="Barnard D">D. L. Barnard</name></author><author><name sortKey="Jones, S M" uniqKey="Jones S">S. M. Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smee, D F" uniqKey="Smee D">D. F. Smee</name></author><author><name sortKey="Hurst, B L" uniqKey="Hurst B">B. L. Hurst</name></author><author><name sortKey="Wong, M H" uniqKey="Wong M">M. H. Wong</name></author><author><name sortKey="Bailey, K W" uniqKey="Bailey K">K. W. Bailey</name></author><author><name sortKey="Tarbet, E B" uniqKey="Tarbet E">E. B. Tarbet</name></author><author><name sortKey="Morrey, J D" uniqKey="Morrey J">J. D. Morrey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stachulski, A V" uniqKey="Stachulski A">A. V. Stachulski</name></author><author><name sortKey="Santoro, M G" uniqKey="Santoro M">M. G. Santoro</name></author><author><name sortKey="Piacentini, S" uniqKey="Piacentini S">S. Piacentini</name></author><author><name sortKey="Belardo, G" uniqKey="Belardo G">G. Belardo</name></author><author><name sortKey="Frazia, S" uniqKey="Frazia S">S. Frazia</name></author><author><name sortKey="Pidathala, C" uniqKey="Pidathala C">C. Pidathala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z. Sun</name></author><author><name sortKey="Pan, Y" uniqKey="Pan Y">Y. Pan</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takashita, E" uniqKey="Takashita E">E. Takashita</name></author><author><name sortKey="Ejima, M" uniqKey="Ejima M">M. Ejima</name></author><author><name sortKey="Ogawa, R" uniqKey="Ogawa R">R. Ogawa</name></author><author><name sortKey="Fujisaki, S" uniqKey="Fujisaki S">S. Fujisaki</name></author><author><name sortKey="Neumann, G" uniqKey="Neumann G">G. Neumann</name></author><author><name sortKey="Furuta, Y" uniqKey="Furuta Y">Y. Furuta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takashita, E" uniqKey="Takashita E">E. Takashita</name></author><author><name sortKey="Kiso, M" uniqKey="Kiso M">M. Kiso</name></author><author><name sortKey="Fujisaki, S" uniqKey="Fujisaki S">S. Fujisaki</name></author><author><name sortKey="Yokoyama, M" uniqKey="Yokoyama M">M. Yokoyama</name></author><author><name sortKey="Nakamura, K" uniqKey="Nakamura K">K. Nakamura</name></author><author><name sortKey="Shirakura, M" uniqKey="Shirakura M">M. Shirakura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takashita, E" uniqKey="Takashita E">E. Takashita</name></author><author><name sortKey="Morita, H" uniqKey="Morita H">H. Morita</name></author><author><name sortKey="Ogawa, R" uniqKey="Ogawa R">R. Ogawa</name></author><author><name sortKey="Nakamura, K" uniqKey="Nakamura K">K. Nakamura</name></author><author><name sortKey="Fujisaki, S" uniqKey="Fujisaki S">S. Fujisaki</name></author><author><name sortKey="Shirakura, M" uniqKey="Shirakura M">M. Shirakura</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taleb, S A" uniqKey="Taleb S">S. A. Taleb</name></author><author><name sortKey="Al Thani, A A" uniqKey="Al Thani A">A. A. Al Thani</name></author><author><name sortKey="Al Ansari, K" uniqKey="Al Ansari K">K. Al Ansari</name></author><author><name sortKey="Yassine, H M" uniqKey="Yassine H">H. M. Yassine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tarbet, E B" uniqKey="Tarbet E">E. B. Tarbet</name></author><author><name sortKey="Maekawa, M" uniqKey="Maekawa M">M. Maekawa</name></author><author><name sortKey="Furuta, Y" uniqKey="Furuta Y">Y. Furuta</name></author><author><name sortKey="Babu, Y S" uniqKey="Babu Y">Y. S. Babu</name></author><author><name sortKey="Morrey, J D" uniqKey="Morrey J">J. D. Morrey</name></author><author><name sortKey="Smee, D F" uniqKey="Smee D">D. F. Smee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tharakaraman, K" uniqKey="Tharakaraman K">K. Tharakaraman</name></author><author><name sortKey="Subramanian, V" uniqKey="Subramanian V">V. Subramanian</name></author><author><name sortKey="Cain, D" uniqKey="Cain D">D. Cain</name></author><author><name sortKey="Sasisekharan, V" uniqKey="Sasisekharan V">V. Sasisekharan</name></author><author><name sortKey="Sasisekharan, R" uniqKey="Sasisekharan R">R. Sasisekharan</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Tian, D" uniqKey="Tian D">D. Tian</name></author><author><name sortKey="Battles, M B" uniqKey="Battles M">M. B. Battles</name></author><author><name sortKey="Moin, S M" uniqKey="Moin S">S. M. Moin</name></author><author><name sortKey="Chen, M" uniqKey="Chen M">M. Chen</name></author><author><name sortKey="Modjarrad, K" uniqKey="Modjarrad K">K. Modjarrad</name></author><author><name sortKey="Kumar, A" uniqKey="Kumar A">A. Kumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tilmanis, D" uniqKey="Tilmanis D">D. Tilmanis</name></author><author><name sortKey="Van Baalen, C" uniqKey="Van Baalen C">C. Van Baalen</name></author><author><name sortKey="Oh, D Y" uniqKey="Oh D">D. Y. Oh</name></author><author><name sortKey="Rossignol, J F" uniqKey="Rossignol J">J. F. Rossignol</name></author><author><name sortKey="Hurt, A C" uniqKey="Hurt A">A. C. Hurt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toovey, S" uniqKey="Toovey S">S. Toovey</name></author><author><name sortKey="Wu, J" uniqKey="Wu J">J. Wu</name></author><author><name sortKey="Wang, V" uniqKey="Wang V">V. Wang</name></author><author><name sortKey="Griffin, P" uniqKey="Griffin P">P. Griffin</name></author><author><name sortKey="Lau, A" uniqKey="Lau A">A. Lau</name></author><author><name sortKey="Elliot, S" uniqKey="Elliot S">S. Elliot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trevejo, J M" uniqKey="Trevejo J">J. M. Trevejo</name></author><author><name sortKey="Asmal, M" uniqKey="Asmal M">M. Asmal</name></author><author><name sortKey="Vingerhoets, J" uniqKey="Vingerhoets J">J. Vingerhoets</name></author><author><name sortKey="Polo, R" uniqKey="Polo R">R. Polo</name></author><author><name sortKey="Robertson, S" uniqKey="Robertson S">S. Robertson</name></author><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Triana Baltzer, G B" uniqKey="Triana Baltzer G">G. B. Triana-Baltzer</name></author><author><name sortKey="Babizki, M" uniqKey="Babizki M">M. Babizki</name></author><author><name sortKey="Chan, M C" uniqKey="Chan M">M. C. Chan</name></author><author><name sortKey="Wong, A C" uniqKey="Wong A">A. C. Wong</name></author><author><name sortKey="Aschenbrenner, L M" uniqKey="Aschenbrenner L">L. M. Aschenbrenner</name></author><author><name sortKey="Campbell, E R" uniqKey="Campbell E">E. R. Campbell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Triana Baltzer, G B" uniqKey="Triana Baltzer G">G. B. Triana-Baltzer</name></author><author><name sortKey="Gubareva, L V" uniqKey="Gubareva L">L. V. Gubareva</name></author><author><name sortKey="Nicholls, J M" uniqKey="Nicholls J">J. M. Nicholls</name></author><author><name sortKey="Pearce, M B" uniqKey="Pearce M">M. B. Pearce</name></author><author><name sortKey="Mishin, V P" uniqKey="Mishin V">V. P. Mishin</name></author><author><name sortKey="Belser, J A" uniqKey="Belser J">J. A. Belser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Triana Baltzer, G B" uniqKey="Triana Baltzer G">G. B. Triana-Baltzer</name></author><author><name sortKey="Sanders, R L" uniqKey="Sanders R">R. L. Sanders</name></author><author><name sortKey="Hedlund, M" uniqKey="Hedlund M">M. Hedlund</name></author><author><name sortKey="Jensen, K A" uniqKey="Jensen K">K. A. Jensen</name></author><author><name sortKey="Aschenbrenner, L M" uniqKey="Aschenbrenner L">L. M. Aschenbrenner</name></author><author><name sortKey="Larson, J L" uniqKey="Larson J">J. L. Larson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uehara, T" uniqKey="Uehara T">T. Uehara</name></author><author><name sortKey="Keiko, K" uniqKey="Keiko K">K. Keiko</name></author><author><name sortKey="Kawaguchi, K" uniqKey="Kawaguchi K">K. Kawaguchi</name></author><author><name sortKey="Sato, C" uniqKey="Sato C">C. Sato</name></author><author><name sortKey="Ishida, T" uniqKey="Ishida T">T. Ishida</name></author><author><name sortKey="Hirotsu, N" uniqKey="Hirotsu N">N. Hirotsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Heeke, G" uniqKey="Van Heeke G">G. Van Heeke</name></author><author><name sortKey="Allosery, K" uniqKey="Allosery K">K. Allosery</name></author><author><name sortKey="De Brabandere, V" uniqKey="De Brabandere V">V. De Brabandere</name></author><author><name sortKey="De Smedt, T" uniqKey="De Smedt T">T. De Smedt</name></author><author><name sortKey="Detalle, L" uniqKey="Detalle L">L. Detalle</name></author><author><name sortKey="De Fougerolles, A" uniqKey="De Fougerolles A">A. De Fougerolles</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Pielak, R M" uniqKey="Pielak R">R. M. Pielak</name></author><author><name sortKey="Mcclintock, M A" uniqKey="Mcclintock M">M. A. McClintock</name></author><author><name sortKey="Chou, J J" uniqKey="Chou J">J. J. Chou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wasserman, R L" uniqKey="Wasserman R">R. L. Wasserman</name></author><author><name sortKey="Greener, B N" uniqKey="Greener B">B. N. Greener</name></author><author><name sortKey="Mond, J" uniqKey="Mond J">J. Mond</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Watanabe, T" uniqKey="Watanabe T">T. Watanabe</name></author><author><name sortKey="Kiso, M" uniqKey="Kiso M">M. Kiso</name></author><author><name sortKey="Fukuyama, S" uniqKey="Fukuyama S">S. Fukuyama</name></author><author><name sortKey="Nakajima, N" uniqKey="Nakajima N">N. Nakajima</name></author><author><name sortKey="Imai, M" uniqKey="Imai M">M. Imai</name></author><author><name sortKey="Yamada, S" uniqKey="Yamada S">S. Yamada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wernery, U" uniqKey="Wernery U">U. Wernery</name></author><author><name sortKey="Lau, S K" uniqKey="Lau S">S. K. Lau</name></author><author><name sortKey="Woo, P C" uniqKey="Woo P">P. C. Woo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Widagdo, W" uniqKey="Widagdo W">W. Widagdo</name></author><author><name sortKey="Okba, N M A" uniqKey="Okba N">N. M. A. Okba</name></author><author><name sortKey="Stalin Raj, V" uniqKey="Stalin Raj V">V. Stalin Raj</name></author><author><name sortKey="Haagmans, B L" uniqKey="Haagmans B">B. L. Haagmans</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Wu, X X" uniqKey="Wu X">X. X. Wu</name></author><author><name sortKey="Gao, H N" uniqKey="Gao H">H. N. Gao</name></author><author><name sortKey="Wu, H B" uniqKey="Wu H">H. B. Wu</name></author><author><name sortKey="Peng, X M" uniqKey="Peng X">X. M. Peng</name></author><author><name sortKey="Ou, H L" uniqKey="Ou H">H. L. Ou</name></author><author><name sortKey="Li, L J" uniqKey="Li L">L. J. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name></author><author><name sortKey="Pfarr, D S" uniqKey="Pfarr D">D. S. Pfarr</name></author><author><name sortKey="Johnson, S" uniqKey="Johnson S">S. Johnson</name></author><author><name sortKey="Brewah, Y A" uniqKey="Brewah Y">Y. A. Brewah</name></author><author><name sortKey="Woods, R M" uniqKey="Woods R">R. M. Woods</name></author><author><name sortKey="Patel, N K" uniqKey="Patel N">N. K. Patel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wyde, P R" uniqKey="Wyde P">P. R. Wyde</name></author><author><name sortKey="Chetty, S N" uniqKey="Chetty S">S. N. Chetty</name></author><author><name sortKey="Timmerman, P" uniqKey="Timmerman P">P. Timmerman</name></author><author><name sortKey="Gilbert, B E" uniqKey="Gilbert B">B. E. Gilbert</name></author><author><name sortKey="Andries, K" uniqKey="Andries K">K. Andries</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wyde, P R" uniqKey="Wyde P">P. R. Wyde</name></author><author><name sortKey="Laquerre, S" uniqKey="Laquerre S">S. Laquerre</name></author><author><name sortKey="Chetty, S N" uniqKey="Chetty S">S. N. Chetty</name></author><author><name sortKey="Gilbert, B E" uniqKey="Gilbert B">B. E. Gilbert</name></author><author><name sortKey="Nitz, T J" uniqKey="Nitz T">T. J. Nitz</name></author><author><name sortKey="Pevear, D C" uniqKey="Pevear D">D. C. Pevear</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xing, Y" uniqKey="Xing Y">Y. Xing</name></author><author><name sortKey="Proesmans, M" uniqKey="Proesmans M">M. Proesmans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yip, T F" uniqKey="Yip T">T. F. Yip</name></author><author><name sortKey="Selim, A S M" uniqKey="Selim A">A. S. M. Selim</name></author><author><name sortKey="Lian, I" uniqKey="Lian I">I. Lian</name></author><author><name sortKey="Lee, S M" uniqKey="Lee S">S. M. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zenilman, J M" uniqKey="Zenilman J">J. M. Zenilman</name></author><author><name sortKey="Fuchs, E J" uniqKey="Fuchs E">E. J. Fuchs</name></author><author><name sortKey="Hendrix, C W" uniqKey="Hendrix C">C. W. Hendrix</name></author><author><name sortKey="Radebaugh, C" uniqKey="Radebaugh C">C. Radebaugh</name></author><author><name sortKey="Jurao, R" uniqKey="Jurao R">R. Jurao</name></author><author><name sortKey="Nayak, S U" uniqKey="Nayak S">S. U. Nayak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Perera, R A" uniqKey="Perera R">R. A. Perera</name></author><author><name sortKey="Kayali, G" uniqKey="Kayali G">G. Kayali</name></author><author><name sortKey="Meyerholz, D" uniqKey="Meyerholz D">D. Meyerholz</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Peiris, M" uniqKey="Peiris M">M. Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, Q" uniqKey="Zhu Q">Q. Zhu</name></author><author><name sortKey="Mcauliffe, J M" uniqKey="Mcauliffe J">J. M. McAuliffe</name></author><author><name sortKey="Patel, N K" uniqKey="Patel N">N. K. Patel</name></author><author><name sortKey="Palmer Hill, F J" uniqKey="Palmer Hill F">F. J. Palmer-Hill</name></author><author><name sortKey="Yang, C F" uniqKey="Yang C">C.-F. Yang</name></author><author><name sortKey="Liang, B" uniqKey="Liang B">B. Liang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhurilo, N I" uniqKey="Zhurilo N">N. I. Zhurilo</name></author><author><name sortKey="Chudinov, M V" uniqKey="Chudinov M">M. V. Chudinov</name></author><author><name sortKey="Matveev, A V" uniqKey="Matveev A">A. V. Matveev</name></author><author><name sortKey="Smirnova, O S" uniqKey="Smirnova O">O. S. Smirnova</name></author><author><name sortKey="Konstantinova, I D" uniqKey="Konstantinova I">I. D. Konstantinova</name></author><author><name sortKey="Miroshnikov, A I" uniqKey="Miroshnikov A">A. I. Miroshnikov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zorc, J J" uniqKey="Zorc J">J. J. Zorc</name></author><author><name sortKey="Hall, C B" uniqKey="Hall C">C. B. Hall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Chan, J F" uniqKey="Chan J">J. F. Chan</name></author><author><name sortKey="Azhar, E I" uniqKey="Azhar E">E. I. Azhar</name></author><author><name sortKey="Hui, D S" uniqKey="Hui D">D. S. Hui</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K. Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Hui, D S" uniqKey="Hui D">D. S. Hui</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Microbiol</journal-id><journal-id journal-id-type="iso-abbrev">Front Microbiol</journal-id><journal-id journal-id-type="publisher-id">Front. Microbiol.</journal-id><journal-title-group><journal-title>Frontiers in Microbiology</journal-title></journal-title-group><issn pub-type="epub">1664-302X</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31275265</article-id><article-id pub-id-type="pmc">6594388</article-id><article-id pub-id-type="doi">10.3389/fmicb.2019.01327</article-id><article-categories><subj-group subj-group-type="heading"><subject>Microbiology</subject><subj-group><subject>Review</subject></subj-group></subj-group></article-categories><title-group><article-title>Overview of Current Therapeutics and Novel Candidates Against Influenza, Respiratory Syncytial Virus, and Middle East Respiratory Syndrome Coronavirus Infections</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Behzadi</surname><given-names>Mohammad Amin</given-names></name><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/698067/overview"></uri></contrib><contrib contrib-type="author"><name><surname>Leyva-Grado</surname><given-names>Victor H.</given-names></name><xref rid="c001" ref-type="corresp"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/665743/overview"></uri></contrib></contrib-group><aff><institution>Department of Microbiology, Icahn School of Medicine at Mount Sinai</institution>,<addr-line>New York, NY</addr-line>,<country>United States</country></aff><author-notes><fn id="fn1" fn-type="edited-by"><p>Edited by: Daniel Roberto Perez, University of Georgia, United States</p></fn><fn id="fn2" fn-type="edited-by"><p>Reviewed by: Luis Martinez-Sobrido, University of Rochester, United States; Hana Maria Dobrovolny, Texas Christian University, United States</p></fn><corresp id="c001">*Correspondence: Victor H. Leyva-Grado, <email>victor.leyva-grado@mssm.edu</email></corresp><fn id="fn3" fn-type="other"><p>This article was submitted to Virology, a section of the journal Frontiers in Microbiology</p></fn></author-notes><pub-date pub-type="epub"><day>19</day><month>6</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>10</volume><elocation-id>1327</elocation-id><history><date date-type="received"><day>04</day><month>3</month><year>2019</year></date><date date-type="accepted"><day>28</day><month>5</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 Behzadi and Leyva-Grado.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Behzadi and Leyva-Grado</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p>Emergence and re-emergence of respiratory virus infections represent a significant threat to global public health, as they occur seasonally and less frequently (such as in the case of influenza virus) as pandemic infections. Some of these viruses have been in the human population for centuries and others had recently emerged as a public health problem. Influenza viruses have been affecting the human population for a long time now; however, their ability to rapidly evolve through antigenic drift and antigenic shift causes the emergence of new strains. A recent example of these events is the avian-origin H7N9 influenza virus outbreak currently undergoing in China. Human H7N9 influenza viruses are resistant to amantadines and some strains are also resistant to neuraminidase inhibitors greatly limiting the options for treatment. Respiratory syncytial virus (RSV) may cause a lower respiratory tract infection characterized by bronchiolitis and pneumonia mainly in children and the elderly. Infection with RSV can cause severe disease and even death, imposing a severe burden for pediatric and geriatric health systems worldwide. Treatment for RSV is mainly supportive since the only approved therapy, a monoclonal antibody, is recommended for prophylactic use in high-risk patients. The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging respiratory virus. The virus was first recognized in 2012 and it is associated with a lower respiratory tract disease that is more severe in patients with comorbidities. No licensed vaccines or antivirals have been yet approved for the treatment of MERS-CoV in humans. It is clear that the discovery and development of novel antivirals that can be used alone or in combination with existing therapies to treat these important respiratory viral infections are critical. In this review, we will describe some of the novel therapeutics currently under development for the treatment of these infections.</p></abstract><kwd-group><kwd>antiviral</kwd><kwd>influenza</kwd><kwd>respiratory syncytial virus</kwd><kwd>MERS-coronavirus</kwd><kwd>novel therapeutic agents</kwd></kwd-group><funding-group><award-group><funding-source id="cn1">NIAID-funded Center of Excellence for Influenza Research and Surveillance-CEIRS</funding-source><award-id rid="cn1">HHSN272201400008C</award-id></award-group></funding-group><counts><fig-count count="1"></fig-count><table-count count="1"></table-count><equation-count count="0"></equation-count><ref-count count="173"></ref-count><page-count count="16"></page-count><word-count count="14507"></word-count></counts></article-meta></front><body><sec sec-type="intro" id="sec1"><title>Introduction</title><p>Respiratory viral infections are of global public health concern because they are the most common cause of symptomatic disease leading to a heavy economic burden due to an increased number of sick days (<xref rid="ref22" ref-type="bibr">Borchardt and Rolston, 2012</xref>; <xref rid="ref81" ref-type="bibr">Kim et al., 2017</xref>). In addition, respiratory diseases are one of the most common causes of mortality in developing countries (<xref rid="ref49" ref-type="bibr">Ferkol and Schraufnagel, 2014</xref>). Among the two leading causes of respiratory virus infection are influenza (A and B) viruses and the respiratory syncytial virus (RSV) (<xref rid="ref9" ref-type="bibr">Amarelle et al., 2017</xref>; <xref rid="ref65" ref-type="bibr">Heylen et al., 2017</xref>; <xref rid="ref167" ref-type="bibr">Yip et al., 2018</xref>). Most cases are observed in infants and children although the elderly and the immunocompromised are also at high risk of getting infected and develop severe disease (<xref rid="ref76" ref-type="bibr">Jorquera and Tripp, 2017</xref>).</p><p>While influenza viruses and RSV circulate seasonally between beginning of fall and early spring, the increased numbers of avian influenza (H7N9) in China including highly pathogenic (HP) strains of the virus, the continued outbreaks of the HP avian influenza (HPAI) H5N1 viruses, novel variants of seasonal influenza viruses (H3N2var), and the emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) highlight the serious and important need for developing novel, more effective antiviral therapies (<xref rid="ref173" ref-type="bibr">Zumla et al., 2016</xref>; <xref rid="ref68" ref-type="bibr">International Society for Influenza and other Respiratory Viral Diseases, 2018</xref>). This review article focuses on therapies currently under development for treatment of influenza, RSV, and MERS-CoV infections. We will briefly review drugs that have been approved by the United States Federal Drug Administration (FDA) and then drugs that are in clinical trials (<xref rid="fig1" ref-type="fig">Figure 1</xref>). When available, the clinical trial identifier is included.</p><fig id="fig1" position="float"><label>Figure 1</label><caption><p>Mechanisms of action of different antivirals. A diagram of the virus life cycle of <bold>(A)</bold> influenza virus, <bold>(B)</bold> respiratory syncytial virus, and <bold>(C)</bold> Middle East respiratory syndrome coronavirus, indicating where each therapeutic exerts its antiviral activity. Drugs approved by the FDA are shown in bold.</p></caption><graphic xlink:href="fmicb-10-01327-g001"></graphic></fig></sec><sec id="sec2"><title>Influenza Virus</title><p>Influenza virus is a negative sense, segmented RNA virus that presents a substantial burden to human health. Despite the availability of successful vaccines and antivirals, infection with seasonal influenza viruses is still the cause of 3–5 million cases of severe illnesses and up to 300–650 thousand deaths worldwide (<xref rid="ref159" ref-type="bibr">World Health Organization, 2017</xref>). In the US alone, it is estimated that seasonal influenza affects up to 9 million people a year resulting in 12,000–56,000 deaths annually (<xref rid="ref28" ref-type="bibr">Centers for Disease Control and Prevention, 2018c</xref>). The economic burden is estimated to be in the tens of billions of dollars (<xref rid="ref117" ref-type="bibr">Putri et al., 2018</xref>). In addition, pandemic influenza outbreaks emerge at unpredictable intervals causing increased morbidity, mortality, and a negative economic impact (<xref rid="ref47" ref-type="bibr">Erbelding et al., 2018</xref>).</p><sec id="sec3"><title>Currently Federal Drug Administration-Approved Anti-influenza Antivirals</title><p>Briefly, these drugs can be divided in three groups: the M2 ion channel blockers, the neuraminidase inhibitors (NAIs), and the virus polymerase inhibitors. Amantadine and rimantadine are adamantane derivatives that inhibit viral replication by blocking the proton conductivity of the M2 ion channel preventing delivery of the virus ribonucleoprotein in the cytoplasm (<xref rid="ref126" ref-type="bibr">Schnell and Chou, 2008</xref>; <xref rid="ref69" ref-type="bibr">Ison, 2017</xref>). These compounds are specific for influenza A viruses since the M2 protein of influenza B viruses is structurally different (<xref rid="ref153" ref-type="bibr">Wang et al., 2009</xref>; <xref rid="ref116" ref-type="bibr">Pielak and Chou, 2011</xref>). In recent past seasons, surveillance studies reported high levels of resistance (>99%) to adamantanes among circulating influenza A(H3N2) and influenza A(H1N1)pdm09 viruses, and the centers for disease control and prevention (CDC) does not recommend these compounds for antiviral treatment or chemoprophylaxis of currently circulating influenza A viruses (<xref rid="ref26" ref-type="bibr">Centers for Disease Control and Prevention, 2018a</xref>). Development of NAI started in the early 1970s with derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (<xref rid="ref111" ref-type="bibr">Palese et al., 1970</xref>), although it was not until 1999 that the first NAI was approved for use in humans (<xref rid="ref32" ref-type="bibr">Chaudhuri et al., 2018</xref>). The NAI binds to the neuraminidase of the virus and prevents its cleavage, thus inhibiting the release of new virus particles (<xref rid="ref69" ref-type="bibr">Ison, 2017</xref>). NAIs currently approved by the FDA include: oseltamivir, zanamivir, and peramivir. Oseltamivir acid is a pro-drug indicated for oral administration. Once in the gastrointestinal tract, the pro-dug is rapidly cleaved to the active metabolite, oseltamivir carboxylate (<xref rid="ref81" ref-type="bibr">Kim et al., 2017</xref>). Due to poor oral bioavailability, zanamivir is approved for inhalation delivery with intravenous administration only available by compassionate use (<xref rid="ref69" ref-type="bibr">Ison, 2017</xref>; <xref rid="ref129" ref-type="bibr">Shaw, 2017</xref>). Peramivir also has poor oral bioavailability; therefore, it has been approved for intravenous administration only. Because the drug reaches high concentrations in plasma and respiratory tissues, it has been approved as a single-dose infusion. One of the inherit problems of these drugs is that, in order to be effective, treatment should start within 48 h post-exposure. Antiviral resistance to oseltamivir, zanamivir, and peramivir is very low in currently circulating influenza virus strains, although this can change because several clusters of oseltamivir resistance have been detected in Japan, Australia, and China (<xref rid="ref138" ref-type="bibr">Takashita et al., 2015</xref>; <xref rid="ref4" ref-type="bibr">Alame et al., 2016</xref>; <xref rid="ref84" ref-type="bibr">Koszalka et al., 2017</xref>). Also known as S-033188, baloxavir marboxil (Xofluza®) is a pro-drug that is hydrolyzed <italic>in vivo</italic> to S-033447, the active form that selectively inhibits cap-dependent endonuclease, preventing the initiation of mRNA synthesis of the influenza virus (<xref rid="ref139" ref-type="bibr">Takashita et al., 2018</xref>). This is a potent small molecule that shows activity against several influenza A viruses, including oseltamivir-resistant viruses as well as B viruses (<xref rid="ref106" ref-type="bibr">Noshi et al., 2018</xref>). Preclinical studies demonstrated that treated mice infected with influenza virus were protected from clinical signs and mortality even in a delay of treatment approach (treatment started 4 days post-infection). Furthermore, a subtherapeutic dose of baloxavir in combination with oseltamivir also protected mice from infection and mortality (<xref rid="ref53" ref-type="bibr">Fukao et al., 2018</xref>). In addition, studies in mice infected with avian influenza viruses such as H5N1 or H7N9 also demonstrated protection after oral administration with baloxavir (<xref rid="ref151" ref-type="bibr">Uehara et al., 2016</xref>). A clinical study (NCT02954354) aimed to compare the efficacy of baloxavir with a placebo or oseltamivir in healthy patients infected with influenza demonstrated that the drug was well tolerated and was associated with a significant reduction in viral load compared to the oseltamivir group. Time of alleviation of symptoms was similar to oseltamivir. The currently undergoing clinical program for this drug includes phase 3 clinical trials to determine safety, pharmacokinetics, and efficacy in healthy pediatric participants aged less than 1 year (NCT03653364) or in pediatric patients with influenza-like symptoms (NCT03629184) and a study to assess efficacy and safety of baloxavir in combination with standard-of-care neuraminidase inhibitor in hospitalized participants with severe influenza (NCT03684044). These studies are currently recruiting and expected to be concluded in spring 2020. In Japan, baloxavir has been approved for the treatment of adult and infant patients infected with influenza; while in the US, the drug has just been approved by the FDA for the treatment of acute, uncomplicated influenza in people aged 12 years and older (<xref rid="ref50" ref-type="bibr">Food and Drug Administration, 2018</xref>). The emergence of resistant variants to polymerase inhibitors has been observed and it is conferred by an I38T mutation in the PA polymerase (<xref rid="ref74" ref-type="bibr">Jones et al., 2018</xref>). In the same study, a novel mutation conferring resistance (E23K) was also observed. Both mutations have been encountered during clinical trials for baloxavir (<xref rid="ref63" ref-type="bibr">Hayden et al., 2018</xref>).</p></sec><sec id="sec4"><title>Promising Drug Candidates in the Pipeline</title><p>Given the inherit limitations of these currently approved compounds and the potential risk for the arising of antiviral resistance, there is still an urgent need for developing new anti-influenza drugs. These novel drugs should have some (ideally all) of the following characteristics: effective when delivered late in infection, low propensity for developing antiviral resistance, broad activity (influenza A and B), improved effectiveness compared to the standard of care, and can be easily administered in uncomplicated as well as complicated cases of influenza (<xref rid="ref84" ref-type="bibr">Koszalka et al., 2017</xref>; <xref rid="ref129" ref-type="bibr">Shaw, 2017</xref>). Next, we will summarize the most advanced (phase 2 and 3 clinical trials), promising drug candidates.</p></sec></sec><sec id="sec5"><title>Viral Targeting Candidates</title><sec id="sec6"><title>Antibodies</title><p>New and more efficient technologies for the production of monoclonal antibodies (mAbs) have stimulated the development of novel mAbs-based therapies for influenza and other infectious diseases (<xref rid="ref72" ref-type="bibr">Jin et al., 2017</xref>). A number of broadly neutralizing mAbs targeting the conserved stalk region of the influenza virus hemagglutinin (HA) molecule are currently under development. In addition, a non-neutralizing mAb targeting the virus matrix protein is also in clinical trials.</p><sec id="sec7"><title>CR6261 and CR8020</title><p>CR6261 is directed against a highly conserved helical region in the membrane-proximal stalk of hemagglutinin. <italic>In vitro</italic> studies on this class of mAbs demonstrated neutralization activity across a broad spectrum of influenza A subtypes. CR6261 is protective in mice against lethal doses of H1N1 and H5N1 viruses (<xref rid="ref85" ref-type="bibr">Koudstaal et al., 2009</xref>). A challenge study successfully demonstrated both therapeutic and prophylactic efficacy in the ferret model against a lethal dose of an H5N1 virus (<xref rid="ref51" ref-type="bibr">Friesen et al., 2010</xref>). A clinical trial phase 2 (NCT02371668) aimed to determine if the CR6261 reduces flu disease in people treated with this drug versus a placebo has concluded but results are still not available. CR8020 targets an immunosubdominant, relatively conserved membrane-proximal stalk region of hemagglutinin. The mAb is active against group 2 influenza viruses and has been shown to have neutralization activity against H3, H7, and H10 subtypes both <italic>in vitro</italic> and <italic>in vivo</italic> (<xref rid="ref45" ref-type="bibr">Ekiert et al., 2011</xref>). A phase 2a trial to evaluate the protective efficacy and safety of CR8020 in an influenza challenge model was completed in 2014 (NCT01938352). Unfortunately, a recent study showed that CR8020 targets a region of the HA stalk that is prone to escape, therefore escape mutants are likely to arise (<xref rid="ref142" ref-type="bibr">Tharakaraman et al., 2014</xref>).</p></sec><sec id="sec8"><title>CT-P27</title><p>This product contains two distinct but complementary mAbs that have shown broad efficacy <italic>in vitro</italic> and <italic>in vivo</italic> against different group 1 and group 2 influenza viruses. A phase 2a clinical trial (NCT02071914) was conducted to evaluate the efficacy and safety of CT-P27 in an influenza challenge model. The study concluded in July 2014, however no results were reported. Currently recruiting, a phase 2b clinical trial (NCT03511066) is aimed to evaluate the efficacy and safety of the mAbs combo in comparison to placebo in subjects with acute uncomplicated influenza A infection.</p></sec><sec id="sec9"><title>MEDI8852</title><p>This is a potent, broadly neutralizing investigational human IgG1 mAb targeting a highly conserved stalk region of the HA protein. MEDI8852 has been reported to effectively neutralize all known influenza A HA subtypes (<xref rid="ref77" ref-type="bibr">Kallewaard et al., 2016</xref>). Preclinical studies in animal models have shown efficacy in protecting against H5N1 influenza virus lethal challenges when used alone or in combination with oseltamivir (<xref rid="ref114" ref-type="bibr">Paules et al., 2017</xref>). A phase 2a study (NCT02603952) to evaluate the safety of MEDI8852 in adults with acute, uncomplicated influenza was recently concluded and results demonstrated an acceptable safety profile in this group of patients. In 2016, MEDI8852 received Fast Track designation by the FDA that allows the drug an expedite development and review (<xref rid="ref5" ref-type="bibr">Ali et al., 2018</xref>).</p></sec><sec id="sec10"><title>MHAA4549A</title><p>This is a human monoclonal IgG1 antibody containing a VH 3-30 59 heavy chain paired with a Vκ1-15 light chain (<xref rid="ref96" ref-type="bibr">McBride et al., 2017</xref>). MHAA4549A targets a highly conserved epitope on the stalk region of HA and is capable of neutralizing all tested seasonal human influenza A strains (<xref rid="ref105" ref-type="bibr">Nakamura et al., 2013</xref>). Two mechanisms of action have been described for this mAb, one by binding the HA to avid virus infectivity and two by antibody-dependent cell-mediated cytotoxicity to increase killing of infected cells (<xref rid="ref96" ref-type="bibr">McBride et al., 2017</xref>). Preclinical studies demonstrated efficacy in the mouse model against a diverse group of influenza viruses including group 1 and group 2 strains even when administered 72 h post-infection. In addition, synergism was observed when administered with oseltamivir at 48 h post-infection. Finally, studies in ferrets demonstrated protection against an H5N1 HPAI virus challenge (<xref rid="ref105" ref-type="bibr">Nakamura et al., 2013</xref>). A few clinical trials have been conducted to evaluate safety, pharmacokinetics, and efficacy of MHAA4549A alone or in combination with oseltamivir (<xref rid="ref86" ref-type="bibr">Lim et al., 2016</xref>; <xref rid="ref96" ref-type="bibr">McBride et al., 2017</xref>; <xref rid="ref36" ref-type="bibr">Deng et al., 2018</xref>). Results established that the mAb is well tolerated with a half-life similar to other human antibodies (~23 days) but with a nonlinear nasal pharmacokinetics (<xref rid="ref96" ref-type="bibr">McBride et al., 2017</xref>; <xref rid="ref36" ref-type="bibr">Deng et al., 2018</xref>). Furthermore, treatment significantly reduced viral loads (<xref rid="ref96" ref-type="bibr">McBride et al., 2017</xref>). The most recent clinical trial (NCT02293863) aimed to investigate the safety and clinical activity of a single intravenous (IV) dose of MHAA4549A in adult participants hospitalized with severe influenza A in combination with oseltamivir was recently concluded and results indicated no advantage on any of the primary clinical outcomes evaluated when compared with the standard of care. Furthermore, no significant differences were observed in any of the virologic outcomes evaluated including viral shedding or peak of virus load.</p></sec></sec><sec id="sec11"><title>Virus Polymerase Inhibitors</title><sec id="sec12"><title>Pimodivir</title><p>This is a novel, non-nucleoside polymerase inhibitor that targets the PB2 subunit of influenza A viruses. Targeting the PB2 avoids docking of the 7-methyl GTP cap structure, thus preventing viral RNA synthesis (<xref rid="ref33" ref-type="bibr">Clark et al., 2014</xref>; <xref rid="ref23" ref-type="bibr">Boyd et al., 2015</xref>). The early activity of pimovidir in the cell cycle has shown to improve cell viability compared to oseltamivir (<xref rid="ref24" ref-type="bibr">Byrn et al., 2015</xref>). Furthermore, it is active against a diverse group of influenza A viruses including the H1N1pdm, H5N1, and H7N9 (<xref rid="ref24" ref-type="bibr">Byrn et al., 2015</xref>). Preclinical studies in mice demonstrated protection against a lethal challenge even when given 4 days post-infection with H1N1pdm or H5N1 viruses (<xref rid="ref24" ref-type="bibr">Byrn et al., 2015</xref>). Further studies also showed protection against a lethal challenge using an H3N2 virus (<xref rid="ref133" ref-type="bibr">Smee et al., 2016</xref>). Studies using pimodivir and oseltamivir suggest a potential benefit for a combination therapy (<xref rid="ref147" ref-type="bibr">Trevejo et al., 2018</xref>). A phase 2b clinical study (NCT02342249) treatment with pimodivir significantly decreased viral load over 7 days versus placebo, in adult patients with acute, uncomplicated seasonal influenza A. Recently, pimodivir has received FDA Fast Track designation due to its potential to address an unmet medical need in those who develop influenza A infection complications. A phase 3 clinical trial (NCT03381196) aimed to evaluate the efficacy and safety of pimodivir in combination with oseltamivir in adults at risk of developing complications is currently recruiting patients and it is expected to be concluded in October 2019.</p></sec><sec id="sec13"><title>Favipiravir</title><p>Formerly known as T-705, this substituted pyrazinecarboxamide derivative is an inhibitor of the influenza virus polymerase. As a purine nucleoside analog, favipiravir directly inhibits the activity of the RNA-dependent RNA polymerase (<xref rid="ref55" ref-type="bibr">Furuta et al., 2005</xref>) and it has broad-spectrum activity against all influenza subtypes including those resistant to neuraminidase and M2 inhibitors (<xref rid="ref54" ref-type="bibr">Furuta et al., 2017</xref>). Preclinical studies demonstrated the broad antiviral spectrum of this compound against different human and avian influenza A and B viruses including avian influenza viruses H5N1 and H7N9 (<xref rid="ref130" ref-type="bibr">Sidwell et al., 2007</xref>; <xref rid="ref155" ref-type="bibr">Watanabe et al., 2013</xref>) where it has shown protection and reduction of virus titers in the infected mice. Furthermore, mice treated with favipiravir had a better outcome after an H7N9 infection compared to mice treated with neuraminidase inhibitors (<xref rid="ref155" ref-type="bibr">Watanabe et al., 2013</xref>). Combination therapy studies found that this drug works synergistically with neuraminidase inhibitors to improve lung virus titers, body weight loss, and survival in mice infected with a pandemic H1N1 influenza virus (<xref rid="ref141" ref-type="bibr">Tarbet et al., 2012</xref>) or with an avian influenza virus H5N1 (<xref rid="ref134" ref-type="bibr">Smee et al., 2010</xref>). Favipiravir is approved in Japan, but its use is restricted to patients infected with an influenza virus resistant to NAI or in the event of a pandemic (Toyama Chemical Co. Ltd). These conditions have been put in place due to concerns of teratogenicity, which have been identified in animal experiments. A couple of phase 3 clinical trials aimed to determine the efficacy and safety of favipiravir for the treatment of uncomplicated influenza infection in adults have been completed but the results have not been published yet. A new phase 2a clinical trial study to determine the pharmacokinetics of favipiravir in patients with severe influenza is reported as active but not currently recruiting with estimated study completion date of March 2019 (NCT03394209). This is a very promising broad-spectrum anti-influenza antiviral that also has a broad antiviral activity against several other RNA viruses (<xref rid="ref35" ref-type="bibr">Davidson, 2018</xref>). A couple of caveats may limit the use of this antiviral to compassionate use or in the case of emerging or re-emerging viruses for which a treatment is not available. Favipiravir has the potential for teratogenicity and embryotoxicity and is the reason why it has conditional approval in Japan (<xref rid="ref54" ref-type="bibr">Furuta et al., 2017</xref>). A study of samples obtained for a clinical trial tested the emergence of mutations in viruses obtained from paired patients before and 1 or 2 days after the initiation of treatment showed the emergence of amino acid substitutions in the RNA polymerase subunits. Although these mutations did not significantly reduce the susceptibility to favipiravir (<xref rid="ref137" ref-type="bibr">Takashita et al., 2016</xref>)<italic>, in vitro</italic> escalation studies showed that influenza viruses can adapt to low concentration of the compound which highlights the potential for some influenza virus strains to possibly develop resistance (<xref rid="ref109" ref-type="bibr">Ormond et al., 2017</xref>).</p></sec></sec></sec><sec id="sec14"><title>Host-Targeting Candidates</title><sec id="sec15"><title>Fludase</title><p>Also known as DAS-181, this is a recombinant sialidase composed of the catalytic domain of a bacterial sialidase (<italic>Actinomyces</italic><italic>viscosus</italic>) and the epithelium-anchoring domain of the human protein amphiregulin (<xref rid="ref91" ref-type="bibr">Malakhov et al., 2006</xref>). In the human respiratory tract, cell surface sialic acids are the primary receptors for binding and entry of influenza viruses. Fludase works by removing sialic receptors from the airway epithelium, therefore preventing viral entry into cells of the respiratory epithelium (<xref rid="ref150" ref-type="bibr">Triana-Baltzer et al., 2011</xref>). Preclinical <italic>in vitro</italic> studies show that fludase is a broad-spectrum anti-influenza antiviral with potent antiviral activity against human and avian influenza viruses with no cellular toxicity (<xref rid="ref149" ref-type="bibr">Triana-Baltzer et al., 2009</xref>, <xref rid="ref148" ref-type="bibr">2010</xref>). <italic>In vivo</italic> studies showed that mice can be rescued from influenza infection after treatment with fludase, including after infection with highly pathogenic H5N1 and H7N9 viruses (<xref rid="ref17" ref-type="bibr">Belser et al., 2007</xref>; <xref rid="ref92" ref-type="bibr">Marjuki et al., 2014</xref>, <xref rid="ref93" ref-type="bibr">2015</xref>). In a randomized, double-blind, placebo-controlled phase 2 study conducted to determine the effective dose in healthy adult participants with laboratory-confirmed influenza (NCT01037205), it was observed that treatment with fludase significantly reduces viral load and viral shedding after multiple doses. In addition, no significant adverse effects were observed in the patients that received the treatment (<xref rid="ref103" ref-type="bibr">Moss et al., 2012</xref>). In a phase 1 clinical trial (NCT01651494), it was observed that in longer treatments (more than 7 days), patients developed antibodies against the compound leading to a reduced efficacy (<xref rid="ref168" ref-type="bibr">Zenilman et al., 2015</xref>).</p></sec><sec id="sec16"><title>Nitazoxanide (Alina<sup>®</sup>)</title><p>Nitazoxanide (NTZ) was originally developed and licensed as an antiprotozoal drug for the treatment of enteritis caused by <italic>Cryptosporidium</italic> and <italic>Giardia</italic> infections. Nitazoxanide is a thiazolide compound that is rapidly deacetylated in the blood to the active metabolic form tizoxanide (<xref rid="ref120" ref-type="bibr">Rossignol, 2009</xref>). In addition to its antiparasitic activity, this compound has shown activity against a broad range of viruses including influenza viruses (<xref rid="ref16" ref-type="bibr">Belardo et al., 2015</xref>; <xref rid="ref145" ref-type="bibr">Tilmanis et al., 2017</xref>; <xref rid="ref135" ref-type="bibr">Stachulski et al., 2018</xref>). The mechanism of action against influenza virus is achieved by impairing the trafficking of the viral hemagglutinin (HA) from the endoplasmic reticulum to the Golgi apparatus and by blocking HA terminal glycosylation leading to block maturation of the HA (<xref rid="ref121" ref-type="bibr">Rossignol et al., 2009</xref>). Preclinical studies demonstrated an antiviral activity against different strains of influenza A, and B viruses <italic>in vitro</italic> including avian influenza viruses (<xref rid="ref132" ref-type="bibr">Sleeman et al., 2014</xref>). There are not published studies of the antiviral efficacy of NTZ in animal models, although extensive pharmacological testing has been performed in animals (<xref rid="ref84" ref-type="bibr">Koszalka et al., 2017</xref>). Nitazoxanide is an example of a repurposed drug with a lot of studies in humans, which is facilitating the advancement of this drug as a treatment for influenza virus infection (<xref rid="ref120" ref-type="bibr">Rossignol, 2009</xref>). A phase 2b/3 clinical trial (NCT01227421) aimed to determine the safety and efficacy of NTZ in the treatment of acute uncomplicated influenza established that treatment with 300 mg twice a day for 5 days was well tolerated and it was associated with a reduction of symptoms and infectious viral load (<xref rid="ref60" ref-type="bibr">Haffizulla et al., 2014</xref>). A phase 3 study (NCT03336619) to evaluate the efficacy and safety of 300-mg nitazoxanide tablets (<xref rid="ref135" ref-type="bibr">Stachulski et al., 2018</xref>) in the treatment of uncomplicated influenza was concluded in March 2019 but results have not been posted.</p></sec></sec><sec id="sec17"><title>Respiratory Syncytial Virus</title><p>Respiratory syncytial virus is the most commonly identified cause of acute lower respiratory tract infection in infants, children, immunocompromised adults, and the elderly (<xref rid="ref172" ref-type="bibr">Zorc and Hall, 2010</xref>; <xref rid="ref58" ref-type="bibr">Griffiths et al., 2017</xref>). Since the first isolation of the virus from chimpanzees in 1956 (<xref rid="ref102" ref-type="bibr">Morris et al., 1956</xref>), extensive research has been conducted in epidemiology, diagnosis, and animal models for the infection, but there is no vaccine and only two approved antivirals available against the virus (<xref rid="ref166" ref-type="bibr">Xing and Proesmans, 2019</xref>).</p><p>RSV is a non-segmented virus with negative sense single-stranded RNA genome encoding 11 proteins. Out of those, two surface transmembrane proteins, G and F, have been shown to play a key role in RSV binding and fusion, respectively. The virus is classified into two subtypes: A and B, with about 50% genetic diversity in the G gene and 10% differences in the F gene (<xref rid="ref144" ref-type="bibr">Tian et al., 2017</xref>; <xref rid="ref166" ref-type="bibr">Xing and Proesmans, 2019</xref>). Due to less antigenic variability of the F protein compared with the G protein, this protein is the main target of research for developing antivirals as well as anti-RSV vaccines (<xref rid="ref140" ref-type="bibr">Taleb et al., 2018</xref>).</p><sec id="sec18"><title>Currently Federal Drug Administration-Approved Anti-Respiratory Syncytial Virus Antivirals</title><p>There are only two RSV antiviral drugs approved by the FDA for the treatment or prevention of serious respiratory tract infections caused by RSV: aerosolized ribavirin for treatment and palivizumab (Synagis<sup>®</sup>) for prophylaxis.</p><p>The guanosine analog ribavirin is a broad-spectrum antiviral agent with activity against RSV and other RNA viruses such as hepatitis C and Zika viruses (<xref rid="ref10" ref-type="bibr">Antonini et al., 2018</xref>; <xref rid="ref82" ref-type="bibr">Kim et al., 2018</xref>; <xref rid="ref171" ref-type="bibr">Zhurilo et al., 2018</xref>). The beneficial effect of this drug in inhibiting RSV replication was demonstrated in several studies. Ribavirin showed antiviral activity against RSV and reduced RSV lung titers in infected cotton rats (<xref rid="ref19" ref-type="bibr">Bonavia et al., 2011</xref>). Similarly, significant clinical benefits have been observed in children treated with aerosolized ribavirin early in infection (<xref rid="ref40" ref-type="bibr">Devincenzo, 2000</xref>). However, the clinical application of ribavirin is limited because of its nonspecific anti-RSV activity, risks for potential toxicity, and relatively high cost (<xref rid="ref136" ref-type="bibr">Sun et al., 2013</xref>).</p><p>Palivizumab is a humanized monoclonal antibody found to have strong RSV-neutralizing capability against a range of RSV strains. The palivizumab 24-aa epitope structure on the RSV F protein is well characterized (<xref rid="ref125" ref-type="bibr">Schickli et al., 2015</xref>). The drug has been shown to be effective in preventing RSV-related hospitalizations in children (<xref rid="ref52" ref-type="bibr">Frogel et al., 2008</xref>). Although the efficacy of this antiviral against RSV infection is proven, due to the considerable cost of palivizumab, the usage is limited to the high-risk populations (<xref rid="ref127" ref-type="bibr">Shahabi et al., 2017</xref>) including infants and young children (<xref rid="ref27" ref-type="bibr">Centers for Disease Control and Prevention, 2018b</xref>).</p></sec></sec><sec id="sec19"><title>Promising New Antiviral Candidates in the Pipeline</title><p>In recent years, in addition to the FDA-approved RSV antivirals, a number of alternative strategies against RSV including new recombinant antibodies, nanobodies, small molecules such as fusion inhibitors, nucleoprotein inhibitors, nucleoside analogs, and non-nucleoside inhibitors are being developed.</p><sec id="sec20"><title>Antibodies</title><p>Intravenous polyclonal immunoglobulin (IVIG) is a preparation of human serum that contains high titers of neutralizing antibodies against the virus. Usage of IVIG in severe RSV infections in high-risk children significantly reduced the rate of hospitalizations due to related respiratory infections (<xref rid="ref143" ref-type="bibr">The PREVENT Study Group, 1997</xref>). Currently, new recombinant mAbs against RSV are in different stages of development.</p><sec id="sec21"><title>RI-001 and RI-002</title><p>These are aqueous intravenous polyclonal human immunoglobulin G (IgG) from pools of source plasma of screened healthy adult donors with high levels of RSV-neutralizing antibodies. The results of a phase 1 and a 2 study on RI-001 and RI-002, respectively, demonstrated that the preparation met acceptable pharmacokinetic and safety criteria, and achieved a fold-change increase in titer of anti-RSV neutralizing antibodies in patients (<xref rid="ref154" ref-type="bibr">Wasserman et al., 2017</xref>).</p></sec><sec id="sec22"><title>REGN2222</title><p>REGN2222 is a fully human IgG1 mAb produced in VelocImmune mice that binds specifically to the F protein of RSV. Preclinical studies in cotton rats demonstrated that REGN2222 is effective at reducing RSV viral replication in the lungs (<xref rid="ref59" ref-type="bibr">Gurnett-Bander et al., 2016</xref>). Although the results of two clinical trials in phase 1 in healthy adults showed that the antibody was well tolerated and it had a half-life longer than typical IgG1 mAbs with low immunogenicity (<xref rid="ref131" ref-type="bibr">Sivapalasingam et al., 2015</xref>), the results of a recent phase 3 trial in preterm infants revealed that this mAb did not meet its primary endpoint of preventing RSV.</p></sec><sec id="sec23"><title>MEDI8897</title><p>MEDI8897 is a recombinant human IgG1κ mAb with an engineered Fc region to have a longer serum half-life and designed for prevention of lower respiratory tract illness (LRTI) caused by RSV. The antibody binds to the prefusion conformation of the F protein of RSV. The results of placebo-controlled studies in healthy adults and healthy preterm infants showed an increase in the mean half-life of MEDI8897. Moreover, the safety profile of MEDI8897 was similar to placebo (<xref rid="ref57" ref-type="bibr">Griffin et al., 2017</xref>; <xref rid="ref43" ref-type="bibr">Domachowske et al., 2018</xref>). To evaluate the efficacy of this mAb in preventing infection, further clinical studies are still needed in the target population of infants entering their first RSV season.</p></sec><sec id="sec24"><title>ALX-0171</title><p>ALX-0171, the first nanobody developed for treatment of RSV infection, is a trivalent nanobody (42 kDa) that binds the antigenic site II of the RSV F protein and neutralizes both subtypes of RSV. <italic>In vitro</italic> neutralization efficiency of ALX-0171 is greater than palivizumab (<xref rid="ref38" ref-type="bibr">Detalle et al., 2016</xref>). Preclinical studies in cotton rats and neonatal lambs have indicated that ALX-0171 is highly effective in reducing both nasal and lung RSV titers (<xref rid="ref62" ref-type="bibr">Hanton et al., 2012</xref>; <xref rid="ref37" ref-type="bibr">Detalle et al., 2014</xref>). The results of phase 1 and 2 clinical studies demonstrated that inhaled ALX-0171 inhibited RSV replication and reduced viral load compared to placebo. ALX-0171 is currently in clinical trials (NCT03418571) to treat infants hospitalized with RSV infection (<xref rid="ref152" ref-type="bibr">Van Heeke et al., 2017</xref>).</p></sec><sec id="sec25"><title>mAb 131-2G</title><p>131-2G is a murine mAb that binds to the central conserved region of the RSV G protein and interferes with the attachment process by blocking the G protein from binding to CX3CR1 (<xref rid="ref73" ref-type="bibr">Johnson et al., 2015</xref>). RSV-challenged mice studies showed that early treatment with this mAb reduced both pulmonary inflammation and lung virus titers (<xref rid="ref64" ref-type="bibr">Haynes et al., 2009</xref>). Clinical studies are needed to evaluate the safety and efficacy of this antiviral in humans.</p></sec><sec id="sec26"><title>Motavizumab</title><p>Motavizumab is a recombinant humanized mAb that binds to a 24-residue, linear, conformational epitope FFL on the RSV F glycoprotein (<xref rid="ref170" ref-type="bibr">Zhu et al., 2011</xref>). Preclinical studies in cotton rats demonstrated that the mAb decreased RSV titers more than 50 times in lungs in comparison to palivizumab (<xref rid="ref163" ref-type="bibr">Wu et al., 2007</xref>). Phase 1 and 2 clinical trials showed that motavizumab is well tolerated in healthy adults and premature infants as well as in high-risk children with chronic lung disease of prematurity (<xref rid="ref1" ref-type="bibr">Abarca et al., 2009</xref>; <xref rid="ref107" ref-type="bibr">O’Brien et al., 2015</xref>). The results of a recent phase 3 clinical trial to prevent serious RSV disease in healthy term infants indicated that motavizumab reduced the proportion of infants admitted to the hospital with RSV (<xref rid="ref107" ref-type="bibr">O’Brien et al., 2015</xref>).</p></sec></sec><sec id="sec27"><title>Fusion Inhibitors (Small Molecules)</title><p>Numerous studies have evaluated the virus-host interactions to determine the viral and host factors that contribute to replication of viruses. For RSV replication, both the co-receptors that become localized on the epithelium in response to virus-mediated signals and the RSV F protein contribute to this process (<xref rid="ref66" ref-type="bibr">Hotard et al., 2015</xref>). Most antiviral small molecules that bind to the F protein can block membrane fusion and viral penetration, and subsequently inhibit RSV replication (<xref rid="ref14" ref-type="bibr">Battles et al., 2016</xref>).</p><sec id="sec28"><title>GS-5806</title><p>GS-5806 is an orally bioavailable RSV fusion inhibitor that has been shown to prevent RSV entry by blocking the virus-cell fusion process (<xref rid="ref124" ref-type="bibr">Samuel et al., 2015</xref>). In a preclinical study conducted in cotton rats, an efficient bioavailability and penetration of the drug in lung tissue were observed. The results of a clinical study in healthy volunteers experimentally infected with RSV indicated that oral administration of GS-5806 resulted in reduction of viral load and disease severity (<xref rid="ref89" ref-type="bibr">Mackman et al., 2015</xref>). More clinical trials have been completed in different populations including in RSV-infected hospitalized patients, lung transplant recipients, and in hematopoietic stem cell transplantation recipients, but the results are not available yet. Recently published results for phase 2b trials in hospitalized adults with RSV did not show significant reduction in viral load or improvement of clinical outcomes to the disease (<xref rid="ref61" ref-type="bibr">Hanfelt-Goade et al., 2018</xref>). To clarify the efficacy of this drug, further studies are required in infants and children.</p></sec><sec id="sec29"><title>MDT-637</title><p>MDT-637 (VP-14637) is a fusion inhibitor that has been shown to inhibit RSV entry to the cells. Both <italic>in vitro</italic> reports and preclinical studies in cotton rats demonstrated the anti-RSV activity of MDT-637. This compound is effective against both subtypes of RSV (<xref rid="ref81" ref-type="bibr">Kim et al., 2017</xref>). The reformulated form of MDT-637, VP-14637, can be administered by powder inhaler with a quick delivery to the respiratory tract (<xref rid="ref165" ref-type="bibr">Wyde et al., 2005</xref>). The results of phase 1 clinical trials indicated a safety and desirable pharmacokinetic profile of the drug in healthy adults (NCT01475305) (<xref rid="ref81" ref-type="bibr">Kim et al., 2017</xref>).</p></sec><sec id="sec30"><title>JNJ-53718678</title><p>JNJ-678 is a potent RSV-specific fusion inhibitor that has been shown to act as an effective anti-RSV <italic>in vitro</italic> and in animal models (<xref rid="ref123" ref-type="bibr">Roymans et al., 2014</xref>; <xref rid="ref2" ref-type="bibr">Ackermann et al., 2016</xref>). Clinical studies in healthy adults assessed its antiviral efficacy as well as safety. It was shown that JNJ-53718678 reduced RSV viral load, respiratory infections’ severity caused by RSV, and duration of the disease (<xref rid="ref71" ref-type="bibr">Israel et al., 2016</xref>; <xref rid="ref67" ref-type="bibr">Huntjens et al., 2017</xref>). Further studies are needed in infants and children to prove the antiviral activity of this anti-RSV candidate.</p></sec><sec id="sec31"><title>AK-0529</title><p>AK-0529 is a novel compound being developed to inhibit RSV replication by blocking viral entry into the target cells. A placebo-controlled phase 1 clinical trial showed that oral administration of this antiviral is well tolerated among healthy volunteers and meets the standard safety profile (<xref rid="ref146" ref-type="bibr">Toovey et al., 2015</xref>). A phase 2 clinical trial in hospitalized infants infected with RSV is currently underway (NCT02654171).</p></sec><sec id="sec32"><title>TMC353121</title><p>TMC353121, a small substituted benzimidazole RSV fusion inhibitor, is an improved derivative of JNJ-2408068 [a compound with antiviral activity against both RSV A and B, but with long tissue retention times in animal models which created concerns and stopped its further development (<xref rid="ref164" ref-type="bibr">Wyde et al., 2003</xref>; <xref rid="ref20" ref-type="bibr">Bonfanti et al., 2007</xref>)].TMC353121, in contrast to JNJ-2408068, lacks the long tissue retention but maintains its high antiviral activity <italic>in vitro</italic> (<xref rid="ref21" ref-type="bibr">Bonfanti et al., 2008</xref>). Using TMC353121 in preclinical studies in cotton rats (<xref rid="ref122" ref-type="bibr">Rouan et al., 2010</xref>) and African green monkeys (<xref rid="ref70" ref-type="bibr">Ispas et al., 2015</xref>) revealed a reduction in viral loads in a dose-dependent manner and in lung inflammation. Based on these data, TMC353121 could be a drug candidate for treatment of RSV infection; however, safety studies and more clinical evaluations are still needed.</p></sec></sec><sec id="sec33"><title>Nucleoprotein Inhibitors</title><p>One promising area of development revolves around inhibitors of RSV that target the virus nucleoprotein. RSV nucleoprotein is involved in virus assembly and it is crucial for the virus replication. Less genetic variation of this protein among RSV A and B subtypes makes it an amenable molecular target for development of anti-RSV compound (<xref rid="ref34" ref-type="bibr">Collins et al., 2013</xref>).</p><sec id="sec34"><title>RSV-604</title><p>RSV604 is a small molecule with submicromolar RSV activity that was discovered through chemical optimization of an RSV high-throughput screen hit (<xref rid="ref31" ref-type="bibr">Chapman et al., 2007</xref>). It is effective against both RSV A and B replication at a post-entry step. The antiviral mechanism of this compound is related to its binding to the RSV N protein and therefore inhibition of both RNA synthesis and the infectivity of released virus (<xref rid="ref29" ref-type="bibr">Challa et al., 2015</xref>). A phase 2a clinical trial in stem cell transplant patients with RSV infection showed that following treatment with RSV604, plasma exposure reached the 90% effective concentration (EC<sub>90</sub>). In addition, patients had a reduction in viral titers and RSV infection symptoms (<xref rid="ref94" ref-type="bibr">Marty et al., 2007</xref>).</p></sec><sec id="sec35"><title>ALN-RSV01</title><p>ALN-RSV01 is a small interfering RNA (siRNA) with 19 nucleotides targeting a highly conserved region of the RSV nucleoprotein gene. This siRNA has shown to be effective in both prophylaxis and treatment models. Results of a preclinical study in mice indicate that treatment with ALN-RSV01 achieved up to 3-logs reduction in RSV lung titers in comparison to control groups (<xref rid="ref87" ref-type="bibr">Lu et al., 2018</xref>). Intranasal administration of ALN-RSV01 in healthy volunteers inoculated with RSV showed a significant reduction of RSV infection in active drug recipients when compared to the placebo recipients group (<xref rid="ref41" ref-type="bibr">DeVincenzo et al., 2010</xref>). In a phase 2 clinical trial conducted in lung transplant recipients with RSV infection, a good safety profile and positive benefits of this siRNA were observed in reducing the risk of bronchiolitis obliterans syndrome (<xref rid="ref56" ref-type="bibr">Gottlieb et al., 2016</xref>). Further evaluations of this antiviral in naturally RSV-infected children and infants should be established.</p></sec></sec><sec id="sec36"><title>Nucleoside Analog and Non-nucleoside Inhibitors</title><sec id="sec37"><title>ALS-008176</title><p>ALS-008176 (4 chloromethyl-2-deoxy-3,5-di-O-isobutyryl-2-fluorocytidine) is a nucleoside RSV polymerase inhibitor with a high level of oral bioavailability. A preclinical study in African green monkeys infected with RSV and treated orally demonstrated an efficient antiviral activity (<xref rid="ref39" ref-type="bibr">Deval et al., 2015</xref>). A clinical trial in healthy adults experimentally infected with RSV revealed shorter RSV RNA clearance time in the ALS-008176 treated group compared with placebo recipients, and the reduction in RSV viral load ranged from 73 to 88% in nasal washes of ALS-008176 treated individuals (<xref rid="ref42" ref-type="bibr">DeVincenzo et al., 2015</xref>).</p></sec></sec></sec><sec id="sec38"><title>Middle East Respiratory Syndrome</title><p>MERS is an emerging zoonotic disease caused by a virus called MERS coronavirus (MERS-CoV). This virus is an enveloped, single-stranded, positive sense RNA virus with a large genome (approximately 30 kb in length) belonging to the C lineage of <italic>Betacoronavirus</italic> (<xref rid="ref46" ref-type="bibr">Enjuanes et al., 2016</xref>; <xref rid="ref156" ref-type="bibr">Wernery et al., 2017</xref>).</p><p>The disease was first reported in 2012 in the Middle East and since then multiple introductions to the human population have occurred from the dromedary, the only known animal reservoir of MERS-CoV (<xref rid="ref156" ref-type="bibr">Wernery et al., 2017</xref>; <xref rid="ref75" ref-type="bibr">Jordan et al., 2018</xref>; <xref rid="ref110" ref-type="bibr">Paden et al., 2018</xref>). The majority of the 2,374 cases reported up to date (<xref rid="ref161" ref-type="bibr">World Health Organization, 2019</xref>) have occurred in Saudi Arabia (1983 cases). The disease has been reported in 27 countries from different continents with most of them associated with recent travel to the Arabic peninsula (<xref rid="ref112" ref-type="bibr">Park et al., 2019</xref>). Person-to-person transmission has been well documented especially in health care workers and family members and may lead to large outbreaks with a significant impact on public health as observed in the Middle East and Korea (<xref rid="ref80" ref-type="bibr">Ki, 2015</xref>; <xref rid="ref99" ref-type="bibr">Mo and Fisher, 2016</xref>). People from any age can be infected with the virus, although the majority of cases have been observed in adults (<xref rid="ref25" ref-type="bibr">Centers for Disease Control and Prevention, 2017</xref>). Clinical features range from asymptomatic or mild to severe disease and death (<xref rid="ref174" ref-type="bibr">Zumla et al., 2015</xref>; <xref rid="ref118" ref-type="bibr">Rabaan, 2017</xref>). Symptoms may include respiratory illness that can lead to acute respiratory distress syndrome (<xref rid="ref13" ref-type="bibr">Assiri et al., 2013</xref>; <xref rid="ref98" ref-type="bibr">Memish et al., 2013</xref>) and digestive symptoms including nausea, vomiting, and diarrhea (<xref rid="ref25" ref-type="bibr">Centers for Disease Control and Prevention, 2017</xref>) with some patients developing renal failure (<xref rid="ref18" ref-type="bibr">Bermingham et al., 2012</xref>; <xref rid="ref75" ref-type="bibr">Jordan et al., 2018</xref>). The case fatality rate worldwide is 34.6%, while in Saudi Arabia it is 37.5% (<xref rid="ref161" ref-type="bibr">World Health Organization, 2019</xref>).</p><p>To date, there are no licensed vaccines or therapeutics for prevention or treatment of MERS-CoV infection and therapy is focused on supportive care to relive symptoms and in more severe cases to also support function of vital organs (<xref rid="ref100" ref-type="bibr">Modjarrad, 2016</xref>; <xref rid="ref104" ref-type="bibr">Mustafa et al., 2018</xref>). Since no specific treatment is available, supportive therapy and the use of broad-spectrum antivirals are currently the options for treatment (<xref rid="ref119" ref-type="bibr">Rabaan et al., 2017</xref>). A broad range of therapeutics have been used in the clinic to treat MERS-CoV-infected patients, and their use is based on knowledge obtained during the severe acute respiratory syndrome (SARS) outbreak in 2003 and the recent influenza pandemic in 2009 (<xref rid="ref99" ref-type="bibr">Mo and Fisher, 2016</xref>). Furthermore, comprehensive clinical studies are lacking and only field data are available (<xref rid="ref44" ref-type="bibr">Dyall et al., 2017</xref>).</p><p>Therapies that have been used for treatment of patients infected with MERS-CoV include convalescent sera, corticosteroids, and/or antiviral therapeutics including interferons, ribavirin, and protease inhibitors (or combination of members from these groups)(<xref rid="ref8" ref-type="bibr">Al-Tawfiq et al., 2014</xref>; <xref rid="ref115" ref-type="bibr">Petersen et al., 2015</xref>; <xref rid="ref173" ref-type="bibr">Zumla et al., 2016</xref>; <xref rid="ref7" ref-type="bibr">Al-Tawfiq and Memish, 2017</xref>; <xref rid="ref104" ref-type="bibr">Mustafa et al., 2018</xref>). There is a long list of potential therapeutics in preclinical phase that have shown promising results <italic>in vitro</italic> and in animal models. Comprehensive reviews of the current therapeutics under development have been published elsewhere (<xref rid="ref173" ref-type="bibr">Zumla et al., 2016</xref>; <xref rid="ref44" ref-type="bibr">Dyall et al., 2017</xref>; <xref rid="ref119" ref-type="bibr">Rabaan et al., 2017</xref>).</p><sec id="sec39"><title>Convalescent Plasma</title><p>The use of plasma obtained from recovering patients (convalescent plasma) has shown beneficial effects in outbreaks of SARS and influenza virus infections (<xref rid="ref6" ref-type="bibr">Al-Tawfiq et al., 2017</xref>). Studies in these infections indicated that the use of CP can reduce viral loads and mortality (<xref rid="ref90" ref-type="bibr">Mair-Jenkins et al., 2015</xref>; <xref rid="ref162" ref-type="bibr">Wu et al., 2015</xref>). Due to the lack of clinical data demonstrating efficacy in MERS-CoV infection, the use of CP is considered an investigational treatment by the WHO (<xref rid="ref158" ref-type="bibr">World Health Organization, 2014</xref>). Only two cases have been reported to use intravenous immunoglobulin as part of an integral treatment intervention; therefore, a beneficial effect was not readily quantifiable (<xref rid="ref78" ref-type="bibr">Kapoor et al., 2014</xref>; <xref rid="ref12" ref-type="bibr">Arabi et al., 2015</xref>). In preclinical studies, passive transfer of sera from MERS-CoV immune camels to infected mice reduced weight loss and lung histopathology (<xref rid="ref169" ref-type="bibr">Zhao et al., 2015</xref>). A protocol to determine the safety and effectiveness of CP therapy for patients infected with MERS-CoV was recently published (<xref rid="ref12" ref-type="bibr">Arabi et al., 2015</xref>). In this study, the authors concluded that due to the variation in the levels of MERS-CoV-specific immunoglobulins in recovered patients, a large screening will be necessary to obtain sufficient plasma donors. A clinical study was registered based on these findings, but since then, it has been withdrawn (NCT02190799). The use of CP remains as a potential therapeutic intervention but the lack of evidence to prove its safety and efficacy in treating infected patients limits its potential impact (<xref rid="ref104" ref-type="bibr">Mustafa et al., 2018</xref>).</p></sec><sec id="sec40"><title>Polyclonal Human Antibody Produced in Transchromosomic Cattle</title><p>Transchromosomic cattle have been developed to produce fully human polyclonal IgG antibodies following immunization (<xref rid="ref95" ref-type="bibr">Matsushita et al., 2014</xref>). Using this technology, polyclonal sera containing antibodies against the spike protein of MERS-CoV were produced (SAB-301) and demonstrated to be effective in neutralizing the virus <italic>in vitro</italic> and reducing lung virus titers in infected mice (<xref rid="ref88" ref-type="bibr">Luke et al., 2016</xref>). A phase 1 randomized clinical trial aimed to evaluate the safety and tolerability of SAB-301 was conducted (NCT02788188). Results have been published and showed that the polyclonal human antibody is safe and well tolerated in patients at what could be considered therapeutic doses (<xref rid="ref15" ref-type="bibr">Beigel et al., 2018</xref>).</p></sec><sec id="sec41"><title>Monoclonal Antibodies Produced in Humanized Mice</title><p>Using their VelocImmune mice, Regeneron produced fully human mAbs binding the spike protein of MERS-CoV. Two lead mAb candidates (REGN 3051 and REGN 3048) were further characterized <italic>in vitro</italic> and <italic>in vivo</italic> (<xref rid="ref113" ref-type="bibr">Pascal et al., 2015</xref>). <italic>In vitro</italic>, both mAbs potently neutralized the MERS-CoV while <italic>in vivo</italic> studies in a mouse model of infection demonstrated that treatment of infected mice caused a reduction in lung virus titers and histopathology (<xref rid="ref113" ref-type="bibr">Pascal et al., 2015</xref>). A phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single ascending doses of a combination of both mAbs administered IV in healthy adult volunteers is currently underway (NCT03301090).</p></sec><sec id="sec42"><title>Broadly Acting Antivirals</title><p>One of the main strategies implemented in the clinics for the treatment of MERS-CoV is the use of broadly acting antivirals although supportive therapy continues to be the primary approach for treatment (<xref rid="ref100" ref-type="bibr">Modjarrad, 2016</xref>). Antivirals such as interferon and ribavirin that show strong inhibition of MERS-CoV <italic>in vitro</italic> have been used in the clinics with different degrees of success. Ribavirin is a synthetic guanosine nucleoside that interferes with the synthesis of viral mRNA. The best effect has been observed using a combination therapy of interferon (IFN) and ribavirin (<xref rid="ref101" ref-type="bibr">Momattin et al., 2013</xref>). Different type I interferons including IFN-α2b and IFN-β1b have been used in the management of patients with confirmed MERS-CoV infection (<xref rid="ref97" ref-type="bibr">McIntosh, 2017</xref>). In a study using macaques, animals were treated with IFN-α2b and ribavirin staring at 8 h after infection with MERS-CoV (<xref rid="ref48" ref-type="bibr">Falzarano et al., 2013</xref>). The infected animals were euthanized at 72 h post-infection which is the peak of disease in this model. The group that received the combination treatment did not developed overt clinical signs of infection, had reduced levels of pro-inflammatory cytokines, reduction in lung virus titers, and reduction in overall lung pathology compared to the group of macaques that did not receive treatment. Most of the data on the efficacy of this combination therapy are from retrospectives studies (<xref rid="ref99" ref-type="bibr">Mo and Fisher, 2016</xref>; <xref rid="ref97" ref-type="bibr">McIntosh, 2017</xref>). In a study comparing infected patients that received this combination therapy in addition to support therapy, it was observed that these patients had a significantly better survival at day 14 post-laboratory confirmation of the infection (70%) compared to the patients that only received the supportive therapy (29%) (<xref rid="ref108" ref-type="bibr">Omrani and Shalhoub, 2015</xref>). In a case study report of a health worker infected with MERS-CoV, the use of IFN-α2b plus ribavirin was associated with his recovery as well as with a beneficial prophylactic effect in his spouse who only developed a mild respiratory illness (<xref rid="ref79" ref-type="bibr">Khalid et al., 2015</xref>). IFN-β has also been used in combination therapies for the treatment of MERS-CoV infection (<xref rid="ref128" ref-type="bibr">Shalhoub et al., 2015</xref>; <xref rid="ref11" ref-type="bibr">Arabi et al., 2018</xref>). In a retrospective study that analyzed a small cohort of patients with laboratory-confirmed infection, it was observed that treatment with the combination of IFN-β1a and ribavirin did not significantly improve survival (<xref rid="ref128" ref-type="bibr">Shalhoub et al., 2015</xref>). In a different retrospective study, analysis of the data demonstrated that administration of IFN-β improved survival in treated patients. However, after a multivariate analysis, the positive effect was not significant (<xref rid="ref3" ref-type="bibr">Al Ghamdi et al., 2016</xref>). Results vary between different retrospective studies and this is in part due to the presence of comorbidities and most importantly the time for treatment initiation (<xref rid="ref7" ref-type="bibr">Al-Tawfiq and Memish, 2017</xref>), since it has been observed that the window of opportunity is very narrow and only effective when started within the first 48 h of confirmed diagnosis (<xref rid="ref101" ref-type="bibr">Momattin et al., 2013</xref>; <xref rid="ref8" ref-type="bibr">Al-Tawfiq et al., 2014</xref>; <xref rid="ref157" ref-type="bibr">Widagdo et al., 2017</xref>). A case study of a MERS-CoV-infected patient who received ribavirin in combination with lopinavir/ritonavir (Kaletra®), a human immunodeficiency virus antiviral, and IFN-α2a, reported that this regimen was effective to treat the patient (<xref rid="ref83" ref-type="bibr">Kim et al., 2016</xref>). The patient, a 64-year-old male with different comorbidities, started treatment on day 4 post admission and achieved viral clearance just 6 days after initiation of treatment and finally was discharged from the hospital on day 13 after admission (<xref rid="ref83" ref-type="bibr">Kim et al., 2016</xref>). In a recent study, a combination of ribavirin and lopinavir/ritonavir was used as a post-exposure prophylaxis in health care workers who had been exposed to MERS-CoV-infected patients and demonstrated a reduction of 40% in the risk of infection (<xref rid="ref112" ref-type="bibr">Park et al., 2019</xref>). A preclinical study in common marmosets infected with MERS-CoV showed that treatment with a combination of lopinavir/ritonavir and IFN-β1b improved the clinical and pathological outcomes of the infected animals (<xref rid="ref30" ref-type="bibr">Chan et al., 2015</xref>). A phase 2/3 clinical trial NCT02845843 to determine the feasibility, efficacy, and safety of a combination therapy with lopinavir/ritonavir and IFN-β1b for the treatment of MERS-CoV-infected patients was initiated in 2016. The clinical trial was expected to be concluded in July of 2018; however, no results or activity have been reported.</p></sec></sec><sec sec-type="conclusions" id="sec43"><title>Conclusions</title><p>This review summarizes the current antivirals available for the treatment of influenza and RSV along with potential new therapies for these respiratory virus infections (<xref rid="tab1" ref-type="table">Table 1</xref>). It also addresses the current therapies employing broad-spectrum antivirals for the treatment of MERS-CoV-infected patients (<xref rid="tab1" ref-type="table">Table 1</xref>). Greater advances have been achieved in the field of influenza antivirals. Currently, three groups of drugs are approved for the treatment of influenza, including the newly approved viral polymerase inhibitor baloxavir marboxil and only one approved for RSV, the polyclonal palivizumab. Although effective, these drugs have limitations such as a reduced window of opportunity, potential to produce drug-resistant viruses, and high cost (Palivizumab). This highlights the need for more and better antiviral drugs to treat these respiratory infections. MERS-CoV recently emerged as a zoonotic respiratory infection and, therefore, no effective antivirals are approved for treatment. The initial approach has been to follow examples of antiviral therapies used during the recent SARS outbreak; however, as described in this review, the approach using broad-spectrum antivirals has not been very successful.</p><table-wrap id="tab1" position="float"><label>Table 1</label><caption><p>Novel therapeutics currently under development (clinical trials), for the treatment of influenza virus, respiratory syncytial virus (RSV), and Middle East respiratory syndrome coronavirus (MERS-CoV).</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1">Therapeutic compound</th><th align="left" valign="top" rowspan="1" colspan="1">Infectious agent</th><th align="left" valign="top" rowspan="1" colspan="1">Mechanism(s) of action</th><th align="center" valign="top" rowspan="1" colspan="1">Clinical trial phase</th><th align="left" valign="top" rowspan="1" colspan="1">NCT#</th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">CR6261</td><td align="left" valign="top" rowspan="1" colspan="1">Influenza</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits the binding of the virus to cell membrane receptor</td><td align="center" valign="top" rowspan="1" colspan="1">2a</td><td align="left" valign="top" rowspan="1" colspan="1">NCT02371668</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">CT-P27</td><td align="left" valign="top" rowspan="1" colspan="1">Influenza</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits the binding of the virus to cell membrane receptor</td><td align="center" valign="top" rowspan="1" colspan="1">2b</td><td align="left" valign="top" rowspan="1" colspan="1">NCT03511066<break></break>NCT02071914</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MEDI8852</td><td align="left" valign="top" rowspan="1" colspan="1">Influenza</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits the binding of the virus to cell membrane receptor</td><td align="center" valign="top" rowspan="1" colspan="1">2a</td><td align="left" valign="top" rowspan="1" colspan="1">NCT03903718<break></break>NCT03028909<break></break>NCT02603952</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MHAA4549A</td><td align="left" valign="top" rowspan="1" colspan="1">Influenza</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits the binding of the virus to cell membrane receptor</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT01980966<break></break>NCT02623322<break></break>NCT02293863</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Pimodivir</td><td align="left" valign="top" rowspan="1" colspan="1">Influenza</td><td align="left" valign="top" rowspan="1" colspan="1">Prevents viral RNA synthesis</td><td align="center" valign="top" rowspan="1" colspan="1">3</td><td align="left" valign="top" rowspan="1" colspan="1">NCT03381196</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Favipiravir</td><td align="left" valign="top" rowspan="1" colspan="1">Influenza</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits the activity of the RNA-dependent RNA polymerase</td><td align="center" valign="top" rowspan="1" colspan="1">3</td><td align="left" valign="top" rowspan="1" colspan="1">NCT02026349<break></break>NCT02008344</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Fludase</td><td align="left" valign="top" rowspan="1" colspan="1">Influenza</td><td align="left" valign="top" rowspan="1" colspan="1">Prevents viral entry into cells of the respiratory epithelium</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT01037205</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Nitazoxanide</td><td align="left" valign="top" rowspan="1" colspan="1">Influenza</td><td align="left" valign="top" rowspan="1" colspan="1">Impairs the trafficking of the viral hemagglutinin</td><td align="center" valign="top" rowspan="1" colspan="1">3</td><td align="left" valign="top" rowspan="1" colspan="1">NCT03336619</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">RI-001</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits the binding of the virus to cell membrane receptor</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT00632463</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">REGN2222</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Viral fusion protein inhibitor</td><td align="center" valign="top" rowspan="1" colspan="1">3</td><td align="left" valign="top" rowspan="1" colspan="1">NCT02325791</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MEDI8897</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Viral fusion protein inhibitor</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT02878330</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">ALX-0171</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Viral fusion protein inhibitor</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT03418571</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">131-2G</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Interferes with the attachment process by blocking the G protein</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-clinical</td><td align="left" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Motavizumab</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Viral fusion protein inhibitor</td><td align="center" valign="top" rowspan="1" colspan="1">3</td><td align="left" valign="top" rowspan="1" colspan="1">NCT00121108<break></break>NCT00628303<break></break>NCT00129766</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">GS-5806</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Blocks the virus-cell fusion process</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT01756482<break></break>NCT02534350<break></break>NCT02254408<break></break>NCT02254421<break></break>NCT02135614</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">MDT-637</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits virus entry to the target cells</td><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="left" valign="top" rowspan="1" colspan="1">NCT01489306<break></break>NCT01355016<break></break>NCT01556607</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">JNJ-53718678</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Viral fusion protein inhibitor</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT03656510<break></break>NCT03379675<break></break>NCT02387606</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">AK-0529</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits virus entry to the target cells</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT03699202<break></break>NCT02654171</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">TMC353121</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Viral fusion protein inhibitor</td><td align="center" valign="top" rowspan="1" colspan="1">Pre-clinical</td><td align="left" valign="top" rowspan="1" colspan="1">NA</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">RSV-60444</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits RNA synthesis and the infectivity of released viruses</td><td align="center" valign="top" rowspan="1" colspan="1">2a</td><td align="left" valign="top" rowspan="1" colspan="1">NCT00232635</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">ALN-RSV01</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits RNA replication</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT00658086<break></break>NCT01065935<break></break>NCT00496821</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">ALS-008176</td><td align="left" valign="top" rowspan="1" colspan="1">RSV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits RSV polymerase</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT02094365<break></break>NCT02673476</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Convalescent plasma</td><td align="left" valign="top" rowspan="1" colspan="1">MERS-CoV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits virus entry to the target cells</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="left" valign="top" rowspan="1" colspan="1">NCT02190799</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SAB-301</td><td align="left" valign="top" rowspan="1" colspan="1">MERS-CoV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits virus entry to the target cells</td><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="left" valign="top" rowspan="1" colspan="1">NCT02788188</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">REGN 3051 and REGN 3048</td><td align="left" valign="top" rowspan="1" colspan="1">MERS-CoV</td><td align="left" valign="top" rowspan="1" colspan="1">Inhibits virus entry to the target cells</td><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="left" valign="top" rowspan="1" colspan="1">NCT03301090</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Ribavirin</td><td align="left" valign="top" rowspan="1" colspan="1">MERS-CoV</td><td align="left" valign="top" rowspan="1" colspan="1">Interferes with the synthesis of viral mRNA</td><td align="center" valign="top" rowspan="1" colspan="1">1</td><td align="left" valign="top" rowspan="1" colspan="1">NCT02627378</td></tr></tbody></table></table-wrap><p>Great advances have been made in the last few years and several antivirals are currently under development and many have reached early stages in clinical trials. This is a very exciting and evolving field that will continue producing more effective antivirals that are highly needed for the treatment of respiratory viral infections of global public health concern.</p></sec><sec id="sec44"><title>Author Contributions</title><p>MB and VL-G wrote, reviewed, and approved the submitted manuscript.</p><sec id="sec45"><title>Conflict of Interest Statement</title><p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p></sec></sec></body><back><fn-group><fn fn-type="financial-disclosure"><p><bold>Funding.</bold> This work was supported in part by the NIAID-funded Center of Excellence for Influenza Research and Surveillance-CEIRS (Contract HHSN272201400008C).</p></fn></fn-group><ref-list><title>References</title><ref id="ref1"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abarca</surname><given-names>K.</given-names></name><name><surname>Jung</surname><given-names>E.</given-names></name><name><surname>Fernández</surname><given-names>P.</given-names></name><name><surname>Zhao</surname><given-names>L.</given-names></name><name><surname>Harris</surname><given-names>B.</given-names></name><name><surname>Connor</surname><given-names>E. M.</given-names></name><etal></etal></person-group>. (<year>2009</year>). <article-title>Safety, tolerability, pharmacokinetics, and immunogenicity of motavizumab, a humanized, enhanced-potency monoclonal antibody for the prevention of respiratory syncytial virus infection in at-risk children</article-title>. <source>Pediatr. Infect. Dis. J.</source><volume>28</volume>, <fpage>267</fpage>–<lpage>272</lpage>. <pub-id pub-id-type="doi">10.1097/INF.0b013e31818ffd03</pub-id>, PMID: <pub-id pub-id-type="pmid">19258920</pub-id></mixed-citation></ref><ref id="ref2"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Ackermann</surname><given-names>M.</given-names></name><name><surname>Alnajjar</surname><given-names>S.</given-names></name><name><surname>Larios-Mora</surname><given-names>A.</given-names></name><name><surname>Koul</surname><given-names>A.</given-names></name><name><surname>Rigaux</surname><given-names>P.</given-names></name><name><surname>Gallup</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2016</year>). “<article-title>Therapeutic efficacy of JNJ-53718678, a RSV fusion inhibitor, in neonatal lambs</article-title>” in <source>10th international respiratory syncytial virus symposium</source> (<publisher-loc>Argentina</publisher-loc>: <publisher-name>Patagonia</publisher-name>).</mixed-citation></ref><ref id="ref3"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al Ghamdi</surname><given-names>M.</given-names></name><name><surname>Alghamdi</surname><given-names>K. M.</given-names></name><name><surname>Ghandoora</surname><given-names>Y.</given-names></name><name><surname>Alzahrani</surname><given-names>A.</given-names></name><name><surname>Salah</surname><given-names>F.</given-names></name><name><surname>Alsulami</surname><given-names>A.</given-names></name><etal></etal></person-group> (<year>2016</year>). <article-title>Treatment outcomes for patients with middle eastern respiratory syndrome coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia</article-title>. <source>BMC Infect. Dis.</source><volume>16</volume>:<fpage>174</fpage>. <pub-id pub-id-type="doi">10.1186/s12879-016-1492-4</pub-id><pub-id pub-id-type="pmid">27097824</pub-id></mixed-citation></ref><ref id="ref4"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alame</surname><given-names>M. M.</given-names></name><name><surname>Massaad</surname><given-names>E.</given-names></name><name><surname>Zaraket</surname><given-names>H.</given-names></name></person-group> (<year>2016</year>). <article-title>Peramivir: a novel intravenous neuraminidase inhibitor for treatment of acute influenza infections</article-title>. <source>Front. Microbiol.</source><volume>7</volume>:<fpage>450</fpage>. <pub-id pub-id-type="doi">10.3389/fmicb.2016.00450</pub-id>, PMID: <pub-id pub-id-type="pmid">27065996</pub-id></mixed-citation></ref><ref id="ref5"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ali</surname><given-names>S. O.</given-names></name><name><surname>Takas</surname><given-names>T.</given-names></name><name><surname>Nyborg</surname><given-names>A.</given-names></name><name><surname>Shoemaker</surname><given-names>K.</given-names></name><name><surname>Kallewaard</surname><given-names>N. L.</given-names></name><name><surname>Chiong</surname><given-names>R.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>Evaluation of MEDI8852, an anti-influenza A monoclonal antibody, in treating acute uncomplicated influenza</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>62</volume>:<fpage>e00694-18</fpage>. <pub-id pub-id-type="doi">10.1128/AAC.00694-18</pub-id><pub-id pub-id-type="pmid">30150460</pub-id></mixed-citation></ref><ref id="ref6"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al-Tawfiq</surname><given-names>J. A.</given-names></name><name><surname>Alfaraj</surname><given-names>S. H.</given-names></name><name><surname>Altuwaijri</surname><given-names>T. A.</given-names></name><name><surname>Memish</surname><given-names>Z. A.</given-names></name></person-group> (<year>2017</year>). <article-title>A cohort-study of patients suspected for MERS-CoV in a referral hospital in Saudi Arabia</article-title>. <source>J. Infect.</source><volume>75</volume>, <fpage>378</fpage>–<lpage>379</lpage>. <pub-id pub-id-type="doi">10.1016/j.jinf.2017.06.002</pub-id>, PMID: <pub-id pub-id-type="pmid">28606432</pub-id></mixed-citation></ref><ref id="ref7"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al-Tawfiq</surname><given-names>J. A.</given-names></name><name><surname>Memish</surname><given-names>Z. A.</given-names></name></person-group> (<year>2017</year>). <article-title>Update on therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)</article-title>. <source>Expert Rev. Anti-Infect. Ther.</source><volume>15</volume>, <fpage>269</fpage>–<lpage>275</lpage>. <pub-id pub-id-type="doi">10.1080/14787210.2017.1271712</pub-id>, PMID: <pub-id pub-id-type="pmid">27937060</pub-id></mixed-citation></ref><ref id="ref8"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Al-Tawfiq</surname><given-names>J. A.</given-names></name><name><surname>Momattin</surname><given-names>H.</given-names></name><name><surname>Dib</surname><given-names>J.</given-names></name><name><surname>Memish</surname><given-names>Z. A.</given-names></name></person-group> (<year>2014</year>). <article-title>Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study</article-title>. <source>Int. J. Infect. Dis.</source><volume>20</volume>, <fpage>42</fpage>–<lpage>46</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijid.2013.12.003</pub-id>, PMID: <pub-id pub-id-type="pmid">24406736</pub-id></mixed-citation></ref><ref id="ref9"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amarelle</surname><given-names>L.</given-names></name><name><surname>Lecuona</surname><given-names>E.</given-names></name><name><surname>Sznajder</surname><given-names>J. I.</given-names></name></person-group> (<year>2017</year>). <article-title>Anti-influenza treatment: drugs currently used and under development</article-title>. <source>Arch. Bronconeumol.</source><volume>53</volume>, <fpage>19</fpage>–<lpage>26</lpage>. <pub-id pub-id-type="doi">10.1016/j.arbres.2016.07.004</pub-id>, PMID: <pub-id pub-id-type="pmid">27519544</pub-id></mixed-citation></ref><ref id="ref10"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Antonini</surname><given-names>T. M.</given-names></name><name><surname>Coilly</surname><given-names>A.</given-names></name><name><surname>Rossignol</surname><given-names>E.</given-names></name><name><surname>Fougerou-Leurent</surname><given-names>C.</given-names></name><name><surname>Dumortier</surname><given-names>J.</given-names></name><name><surname>Leroy</surname><given-names>V.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Sofosbuvir-based regimens in HIV/HCV Coinfected patients after liver transplantation: results from the ANRS CO23 CUPILT study</article-title>. <source>Transplantation</source><volume>102</volume>, <fpage>119</fpage>–<lpage>126</lpage>. <pub-id pub-id-type="doi">10.1097/TP.0000000000001928</pub-id>, PMID: <pub-id pub-id-type="pmid">28846559</pub-id></mixed-citation></ref><ref id="ref11"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>Y. M.</given-names></name><name><surname>Alothman</surname><given-names>A.</given-names></name><name><surname>Balkhy</surname><given-names>H. H.</given-names></name><name><surname>Al-Dawood</surname><given-names>A.</given-names></name><name><surname>Aljohani</surname><given-names>S.</given-names></name><name><surname>Al Harbi</surname><given-names>S.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>Treatment of Middle East respiratory syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial</article-title>. <source>Trials</source><volume>19</volume>:<fpage>81</fpage>. <pub-id pub-id-type="doi">10.1186/s13063-017-2427-0</pub-id><pub-id pub-id-type="pmid">29382391</pub-id></mixed-citation></ref><ref id="ref12"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>Y.</given-names></name><name><surname>Balkhy</surname><given-names>H.</given-names></name><name><surname>Hajeer</surname><given-names>A. H.</given-names></name><name><surname>Bouchama</surname><given-names>A.</given-names></name><name><surname>Hayden</surname><given-names>F. G.</given-names></name><name><surname>Al-Omari</surname><given-names>A.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol</article-title>. <source>Springerplus</source><volume>4</volume>:<fpage>709</fpage>. <pub-id pub-id-type="doi">10.1186/s40064-015-1490-9</pub-id><pub-id pub-id-type="pmid">26618098</pub-id></mixed-citation></ref><ref id="ref13"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Assiri</surname><given-names>A.</given-names></name><name><surname>Al-Tawfiq</surname><given-names>J. A.</given-names></name><name><surname>Al-Rabeeah</surname><given-names>A. A.</given-names></name><name><surname>Al-Rabiah</surname><given-names>F. A.</given-names></name><name><surname>Al-Hajjar</surname><given-names>S.</given-names></name><name><surname>Al-Barrak</surname><given-names>A.</given-names></name><etal></etal></person-group>. (<year>2013</year>). <article-title>Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study</article-title>. <source>Lancet Infect. Dis.</source><volume>13</volume>, <fpage>752</fpage>–<lpage>761</lpage>. <pub-id pub-id-type="doi">10.1016/S1473-3099(13)70204-4</pub-id>, PMID: <pub-id pub-id-type="pmid">23891402</pub-id></mixed-citation></ref><ref id="ref14"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Battles</surname><given-names>M. B.</given-names></name><name><surname>Langedijk</surname><given-names>J. P.</given-names></name><name><surname>Furmanova-Hollenstein</surname><given-names>P.</given-names></name><name><surname>Chaiwatpongsakorn</surname><given-names>S.</given-names></name><name><surname>Costello</surname><given-names>H. M.</given-names></name><name><surname>Kwanten</surname><given-names>L.</given-names></name><etal></etal></person-group>. (<year>2016</year>). <article-title>Molecular mechanism of respiratory syncytial virus fusion inhibitors</article-title>. <source>Nat. Chem. Biol.</source><volume>12</volume>, <fpage>87</fpage>–<lpage>93</lpage>. <pub-id pub-id-type="doi">10.1038/nchembio.1982</pub-id>, PMID: <pub-id pub-id-type="pmid">26641933</pub-id></mixed-citation></ref><ref id="ref15"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Beigel</surname><given-names>J. H.</given-names></name><name><surname>Voell</surname><given-names>J.</given-names></name><name><surname>Kumar</surname><given-names>P.</given-names></name><name><surname>Raviprakash</surname><given-names>K.</given-names></name><name><surname>Wu</surname><given-names>H.</given-names></name><name><surname>Jiao</surname><given-names>J. A.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study</article-title>. <source>Lancet Infect. Dis.</source><volume>18</volume>, <fpage>410</fpage>–<lpage>418</lpage>. <pub-id pub-id-type="doi">10.1016/S1473-3099(18)30002-1</pub-id>, PMID: <pub-id pub-id-type="pmid">29329957</pub-id></mixed-citation></ref><ref id="ref16"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Belardo</surname><given-names>G.</given-names></name><name><surname>Cenciarelli</surname><given-names>O.</given-names></name><name><surname>La Frazia</surname><given-names>S.</given-names></name><name><surname>Rossignol</surname><given-names>J. F.</given-names></name><name><surname>Santoro</surname><given-names>M. G.</given-names></name></person-group> (<year>2015</year>). <article-title>Synergistic effect of nitazoxanide with neuraminidase inhibitors against influenza A viruses in vitro</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>59</volume>, <fpage>1061</fpage>–<lpage>1069</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.03947-14</pub-id>, PMID: <pub-id pub-id-type="pmid">25451059</pub-id></mixed-citation></ref><ref id="ref17"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Belser</surname><given-names>J. A.</given-names></name><name><surname>Lu</surname><given-names>X.</given-names></name><name><surname>Szretter</surname><given-names>K. J.</given-names></name><name><surname>Jin</surname><given-names>X.</given-names></name><name><surname>Aschenbrenner</surname><given-names>L. M.</given-names></name><name><surname>Lee</surname><given-names>A.</given-names></name><etal></etal></person-group>. (<year>2007</year>). <article-title>DAS181, a novel sialidase fusion protein, protects mice from lethal avian influenza H5N1 virus infection</article-title>. <source>J. Infect. Dis.</source><volume>196</volume>, <fpage>1493</fpage>–<lpage>1499</lpage>. <pub-id pub-id-type="doi">10.1086/522609</pub-id>, PMID: <pub-id pub-id-type="pmid">18008229</pub-id></mixed-citation></ref><ref id="ref18"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bermingham</surname><given-names>A.</given-names></name><name><surname>Chand</surname><given-names>M. A.</given-names></name><name><surname>Brown</surname><given-names>C. S.</given-names></name><name><surname>Aarons</surname><given-names>E.</given-names></name><name><surname>Tong</surname><given-names>C.</given-names></name><name><surname>Langrish</surname><given-names>C.</given-names></name><etal></etal></person-group>. (<year>2012</year>). <article-title>Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012</article-title>. <source>Euro Surveill.</source><volume>17</volume>:<fpage>20290</fpage>. <pub-id pub-id-type="doi">10.2807/ese.17.40.20290-en</pub-id>, PMID: <pub-id pub-id-type="pmid">23078800</pub-id></mixed-citation></ref><ref id="ref19"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bonavia</surname><given-names>A.</given-names></name><name><surname>Franti</surname><given-names>M.</given-names></name><name><surname>Keaney</surname><given-names>E. P.</given-names></name><name><surname>Kuhen</surname><given-names>K.</given-names></name><name><surname>Seepersaud</surname><given-names>M.</given-names></name><name><surname>Radetich</surname><given-names>B.</given-names></name><etal></etal></person-group>. (<year>2011</year>). <article-title>Identification of broad-spectrum antiviral compounds and assessment of the druggability of their target for efficacy against respiratory syncytial virus (RSV)</article-title>. <source>Proc. Natl. Acad. Sci. USA</source><volume>108</volume>, <fpage>6739</fpage>–<lpage>6744</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.1017142108</pub-id>, PMID: <pub-id pub-id-type="pmid">21502533</pub-id></mixed-citation></ref><ref id="ref20"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bonfanti</surname><given-names>J.-F.</given-names></name><name><surname>Doublet</surname><given-names>F.</given-names></name><name><surname>Fortin</surname><given-names>J.</given-names></name><name><surname>Lacrampe</surname><given-names>J.</given-names></name><name><surname>Guillemont</surname><given-names>J.</given-names></name><name><surname>Muller</surname><given-names>P.</given-names></name><etal></etal></person-group>. (<year>2007</year>). <article-title>Selection of a respiratory syncytial virus fusion inhibitor clinical candidate, part 1: improving the pharmacokinetic profile using the structure−property relationship</article-title>. <source>J. Med. Chem.</source><volume>50</volume>, <fpage>4572</fpage>–<lpage>4584</lpage>. <pub-id pub-id-type="doi">10.1021/jm070143x</pub-id>, PMID: <pub-id pub-id-type="pmid">17722899</pub-id></mixed-citation></ref><ref id="ref21"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bonfanti</surname><given-names>J.-F.</given-names></name><name><surname>Meyer</surname><given-names>C.</given-names></name><name><surname>Doublet</surname><given-names>F.</given-names></name><name><surname>Fortin</surname><given-names>J.</given-names></name><name><surname>Muller</surname><given-names>P.</given-names></name><name><surname>Queguiner</surname><given-names>L.</given-names></name><etal></etal></person-group>. (<year>2008</year>). <article-title>Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121)</article-title>. <source>J. Med. Chem.</source><volume>51</volume>, <fpage>875</fpage>–<lpage>896</lpage>. <pub-id pub-id-type="doi">10.1021/jm701284j</pub-id>, PMID: <pub-id pub-id-type="pmid">18254606</pub-id></mixed-citation></ref><ref id="ref22"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Borchardt</surname><given-names>R. A.</given-names></name><name><surname>Rolston</surname><given-names>K. V.</given-names></name></person-group> (<year>2012</year>). <article-title>Respiratory tract infections: emerging viral pathogens</article-title>. <source>JAAPA</source><volume>25</volume>, <fpage>19</fpage>–<lpage>20</lpage>.</mixed-citation></ref><ref id="ref23"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Boyd</surname><given-names>M. J.</given-names></name><name><surname>Bandarage</surname><given-names>U. K.</given-names></name><name><surname>Bennett</surname><given-names>H.</given-names></name><name><surname>Byrn</surname><given-names>R. R.</given-names></name><name><surname>Davies</surname><given-names>I.</given-names></name><name><surname>Gu</surname><given-names>W.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Isosteric replacements of the carboxylic acid of drug candidate VX-787: effect of charge on antiviral potency and kinase activity of azaindole-based influenza PB2 inhibitors</article-title>. <source>Bioorg. Med. Chem. Lett.</source><volume>25</volume>, <fpage>1990</fpage>–<lpage>1994</lpage>. <pub-id pub-id-type="doi">10.1016/j.bmcl.2015.03.013</pub-id>, PMID: <pub-id pub-id-type="pmid">25827523</pub-id></mixed-citation></ref><ref id="ref24"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Byrn</surname><given-names>R. A.</given-names></name><name><surname>Jones</surname><given-names>S. M.</given-names></name><name><surname>Bennett</surname><given-names>H. B.</given-names></name><name><surname>Bral</surname><given-names>C.</given-names></name><name><surname>Clark</surname><given-names>M. P.</given-names></name><name><surname>Jacobs</surname><given-names>M. D.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>59</volume>, <fpage>1569</fpage>–<lpage>1582</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.04623-14</pub-id>, PMID: <pub-id pub-id-type="pmid">25547360</pub-id></mixed-citation></ref><ref id="ref25"><mixed-citation publication-type="other"><person-group person-group-type="author"><collab id="coll1">Centers for Disease Control and Prevention</collab></person-group> (<year>2017</year>). <article-title>Middle East respiratory syndrome (MERS)</article-title>. <comment>Available at:</comment><ext-link ext-link-type="uri" xlink:href="https://www.cdc.gov/coronavirus/mers/index.html">https://www.cdc.gov/coronavirus/mers/index.html</ext-link><comment>(Accessed April 17, 2019)</comment>.</mixed-citation></ref><ref id="ref26"><mixed-citation publication-type="other"><person-group person-group-type="author"><collab id="coll2">Centers for Disease Control and Prevention</collab></person-group> (<year>2018a</year>). <article-title>Influenza antiviral medications: summary for clinicians</article-title>. <comment>Available at:</comment><ext-link ext-link-type="uri" xlink:href="https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm">https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm</ext-link><comment>(Accessed April 17, 2019)</comment>.</mixed-citation></ref><ref id="ref27"><mixed-citation publication-type="other"><person-group person-group-type="author"><collab id="coll3">Centers for Disease Control and Prevention</collab></person-group> (<year>2018b</year>). <article-title>Respiratory syncytial virus (RSV)</article-title>. <comment>Available at:</comment><ext-link ext-link-type="uri" xlink:href="https://www.cdc.gov/rsv/clinical/index.html">https://www.cdc.gov/rsv/clinical/index.html</ext-link><comment>(Accessed June 2016, 2019)</comment>.</mixed-citation></ref><ref id="ref28"><mixed-citation publication-type="other"><person-group person-group-type="author"><collab id="coll4">Centers for Disease Control and Prevention</collab></person-group> (<year>2018c</year>). <article-title>Summary of the 107-2018 Influenza season</article-title>. <comment>Available at:</comment><ext-link ext-link-type="uri" xlink:href="https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm">https://www.cdc.gov/flu/about/season/flu-season-2017-2018.htm</ext-link><comment>(Accessed April 17, 2019)</comment>.</mixed-citation></ref><ref id="ref29"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Challa</surname><given-names>S.</given-names></name><name><surname>Scott</surname><given-names>A. D.</given-names></name><name><surname>Yuzhakov</surname><given-names>O.</given-names></name><name><surname>Zhou</surname><given-names>Y.</given-names></name><name><surname>Tiong-Yip</surname><given-names>C. L.</given-names></name><name><surname>Gao</surname><given-names>N.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Mechanism of action for respiratory syncytial virus inhibitor RSV604</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>59</volume>, <fpage>1080</fpage>–<lpage>1087</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.04119-14</pub-id>, PMID: <pub-id pub-id-type="pmid">25451060</pub-id></mixed-citation></ref><ref id="ref30"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>S. M.</given-names></name><name><surname>Damdinjav</surname><given-names>B.</given-names></name><name><surname>Perera</surname><given-names>R. A.</given-names></name><name><surname>Chu</surname><given-names>D. K.</given-names></name><name><surname>Khishgee</surname><given-names>B.</given-names></name><name><surname>Enkhbold</surname><given-names>B.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Absence of MERS-coronavirus in Bactrian camels, southern Mongolia, November 2014</article-title>. <source>Emerg. Infect. Dis.</source><volume>21</volume>, <fpage>1269</fpage>–<lpage>1271</lpage>. <pub-id pub-id-type="doi">10.3201/eid2107.150178</pub-id>, PMID: <pub-id pub-id-type="pmid">26080032</pub-id></mixed-citation></ref><ref id="ref31"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chapman</surname><given-names>J.</given-names></name><name><surname>Abbott</surname><given-names>E.</given-names></name><name><surname>Alber</surname><given-names>D. G.</given-names></name><name><surname>Baxter</surname><given-names>R. C.</given-names></name><name><surname>Bithell</surname><given-names>S. K.</given-names></name><name><surname>Henderson</surname><given-names>E. A.</given-names></name><etal></etal></person-group>. (<year>2007</year>). <article-title>RSV604, a novel inhibitor of respiratory syncytial virus replication</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>51</volume>, <fpage>3346</fpage>–<lpage>3353</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.00211-07</pub-id>, PMID: <pub-id pub-id-type="pmid">17576833</pub-id></mixed-citation></ref><ref id="ref32"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaudhuri</surname><given-names>S.</given-names></name><name><surname>Symons</surname><given-names>J. A.</given-names></name><name><surname>Deval</surname><given-names>J.</given-names></name></person-group> (<year>2018</year>). <article-title>Innovation and trends in the development and approval of antiviral medicines: 1987–2017 and beyond</article-title>. <source>Antiviral Res.</source><volume>155</volume>, <fpage>76</fpage>–<lpage>88</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2018.05.005</pub-id>, PMID: <pub-id pub-id-type="pmid">29758235</pub-id></mixed-citation></ref><ref id="ref33"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Clark</surname><given-names>M. P.</given-names></name><name><surname>Ledeboer</surname><given-names>M. W.</given-names></name><name><surname>Davies</surname><given-names>I.</given-names></name><name><surname>Byrn</surname><given-names>R. A.</given-names></name><name><surname>Jones</surname><given-names>S. M.</given-names></name><name><surname>Perola</surname><given-names>E.</given-names></name><etal></etal></person-group>. (<year>2014</year>). <article-title>Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2</article-title>. <source>J. Med. Chem.</source><volume>57</volume>, <fpage>6668</fpage>–<lpage>6678</lpage>. <pub-id pub-id-type="doi">10.1021/jm5007275</pub-id>, PMID: <pub-id pub-id-type="pmid">25019388</pub-id></mixed-citation></ref><ref id="ref34"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Collins</surname><given-names>P. L.</given-names></name><name><surname>Fearns</surname><given-names>R.</given-names></name><name><surname>Graham</surname><given-names>B. S.</given-names></name></person-group> (<year>2013</year>). “<article-title>Respiratory syncytial virus: virology, reverse genetics, and pathogenesis of disease</article-title>” in <source>Challenges and opportunities for respiratory syncytial virus vaccines</source>. eds. <person-group person-group-type="editor"><name><surname>Anderson</surname><given-names>L. J.</given-names></name><name><surname>Graham</surname><given-names>S. B.</given-names></name></person-group> (<publisher-loc>Berlin, Heidelberg</publisher-loc>: <publisher-name>Springer-Verlag</publisher-name>), <fpage>3</fpage>–<lpage>38</lpage>.</mixed-citation></ref><ref id="ref35"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Davidson</surname><given-names>S.</given-names></name></person-group> (<year>2018</year>). <article-title>Treating influenza infection, from now and into the future</article-title>. <source>Front. Immunol.</source><volume>9</volume>:<fpage>1946</fpage>. <pub-id pub-id-type="doi">10.3389/fimmu.2018.01946</pub-id>, PMID: <pub-id pub-id-type="pmid">30250466</pub-id></mixed-citation></ref><ref id="ref36"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Deng</surname><given-names>R.</given-names></name><name><surname>Lee</surname><given-names>A. P.</given-names></name><name><surname>Maia</surname><given-names>M.</given-names></name><name><surname>Lim</surname><given-names>J. J.</given-names></name><name><surname>Burgess</surname><given-names>T.</given-names></name><name><surname>Horn</surname><given-names>P.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Pharmacokinetics of MHAA4549A, an anti-influenza A monoclonal antibody, in healthy subjects challenged with influenza A virus in a phase IIa randomized trial</article-title>. <source>Clin. Pharmacokinet.</source><volume>57</volume>, <fpage>367</fpage>–<lpage>377</lpage>. <pub-id pub-id-type="doi">10.1007/s40262-017-0564-y</pub-id>, PMID: <pub-id pub-id-type="pmid">28639229</pub-id></mixed-citation></ref><ref id="ref37"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Detalle</surname><given-names>L.</given-names></name><name><surname>Larios</surname><given-names>A.</given-names></name><name><surname>Gallup</surname><given-names>L.</given-names></name><name><surname>Van Geelen</surname><given-names>A.</given-names></name><name><surname>Duprez</surname><given-names>L.</given-names></name><name><surname>Stohr</surname><given-names>T.</given-names></name></person-group> (<year>2014</year>). “<article-title>Delivery of ALX-0171 by inhalation greatly reduces disease burden in a neonatal lamb RSV infection model</article-title>” in <source>9th international respiratory syncytial virus symposium</source> (<publisher-loc>Cape Town, South Africa</publisher-loc>) <comment><italic>Abstract OP 72.</italic></comment></mixed-citation></ref><ref id="ref38"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Detalle</surname><given-names>L.</given-names></name><name><surname>Stohr</surname><given-names>T.</given-names></name><name><surname>Palomo</surname><given-names>C.</given-names></name><name><surname>Piedra</surname><given-names>P. A.</given-names></name><name><surname>Gilbert</surname><given-names>B. E.</given-names></name><name><surname>Mas</surname><given-names>V.</given-names></name><etal></etal></person-group> (<year>2016</year>). <article-title>Generation and characterization of ALX-0171, a potent novel therapeutic nanobody for the treatment of respiratory syncytial virus infection</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>60</volume>, <fpage>6</fpage>–<lpage>13</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.01802-15</pub-id><pub-id pub-id-type="pmid">26438495</pub-id></mixed-citation></ref><ref id="ref39"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Deval</surname><given-names>J.</given-names></name><name><surname>Hong</surname><given-names>J.</given-names></name><name><surname>Wang</surname><given-names>G.</given-names></name><name><surname>Taylor</surname><given-names>J.</given-names></name><name><surname>Smith</surname><given-names>L. K.</given-names></name><name><surname>Fung</surname><given-names>A.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Molecular basis for the selective inhibition of respiratory syncytial virus RNA polymerase by 2′-fluoro-4′-chloromethyl-cytidine triphosphate</article-title>. <source>PLoS Pathog.</source><volume>11</volume>:<fpage>e1004995</fpage>. <pub-id pub-id-type="doi">10.1371/journal.ppat.1004995</pub-id>, PMID: <pub-id pub-id-type="pmid">26098424</pub-id></mixed-citation></ref><ref id="ref40"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Devincenzo</surname><given-names>J. P.</given-names></name></person-group> (<year>2000</year>). <article-title>Therapy of respiratory syncytial virus infection</article-title>. <source>Pediatr. Infect. Dis. J.</source><volume>19</volume>, <fpage>786</fpage>–<lpage>790</lpage>. <pub-id pub-id-type="doi">10.1097/00006454-200008000-00032</pub-id>, PMID: <pub-id pub-id-type="pmid">10959759</pub-id></mixed-citation></ref><ref id="ref41"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Devincenzo</surname><given-names>J.</given-names></name><name><surname>Lambkin-Williams</surname><given-names>R.</given-names></name><name><surname>Wilkinson</surname><given-names>T.</given-names></name><name><surname>Cehelsky</surname><given-names>J.</given-names></name><name><surname>Nochur</surname><given-names>S.</given-names></name><name><surname>Walsh</surname><given-names>E.</given-names></name><etal></etal></person-group>. (<year>2010</year>). <article-title>A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus</article-title>. <source>Proc. Natl. Acad. Sci. USA</source><volume>107</volume>, <fpage>8800</fpage>–<lpage>8805</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.0912186107</pub-id>, PMID: <pub-id pub-id-type="pmid">20421463</pub-id></mixed-citation></ref><ref id="ref42"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Devincenzo</surname><given-names>J. P.</given-names></name><name><surname>Mcclure</surname><given-names>M. W.</given-names></name><name><surname>Symons</surname><given-names>J. A.</given-names></name><name><surname>Fathi</surname><given-names>H.</given-names></name><name><surname>Westland</surname><given-names>C.</given-names></name><name><surname>Chanda</surname><given-names>S.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Activity of oral ALS-008176 in a respiratory syncytial virus challenge study</article-title>. <source>N. Engl. J. Med.</source><volume>373</volume>, <fpage>2048</fpage>–<lpage>2058</lpage>. <pub-id pub-id-type="doi">10.1056/NEJMoa1413275</pub-id>, PMID: <pub-id pub-id-type="pmid">26580997</pub-id></mixed-citation></ref><ref id="ref43"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Domachowske</surname><given-names>J. B.</given-names></name><name><surname>Khan</surname><given-names>A. A.</given-names></name><name><surname>Esser</surname><given-names>M. T.</given-names></name><name><surname>Jensen</surname><given-names>K.</given-names></name><name><surname>Takas</surname><given-names>T.</given-names></name><name><surname>Villafana</surname><given-names>T.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Safety, tolerability, and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants</article-title>. <source>Pediatr. Infect. Dis. J.</source><volume>37</volume>, <fpage>886</fpage>–<lpage>892</lpage>. <pub-id pub-id-type="doi">10.1097/INF.0000000000001916</pub-id>, PMID: <pub-id pub-id-type="pmid">29373476</pub-id></mixed-citation></ref><ref id="ref44"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dyall</surname><given-names>J.</given-names></name><name><surname>Gross</surname><given-names>R.</given-names></name><name><surname>Kindrachuk</surname><given-names>J.</given-names></name><name><surname>Johnson</surname><given-names>R. F.</given-names></name><name><surname>Olinger</surname><given-names>G. G.</given-names><suffix>Jr.</suffix></name><name><surname>Hensley</surname><given-names>L. E.</given-names></name><etal></etal></person-group>. (<year>2017</year>). <article-title>Middle East respiratory syndrome and severe acute respiratory syndrome: current therapeutic options and potential targets for novel therapies</article-title>. <source>Drugs</source><volume>77</volume>, <fpage>1935</fpage>–<lpage>1966</lpage>. <pub-id pub-id-type="doi">10.1007/s40265-017-0830-1</pub-id>, PMID: <pub-id pub-id-type="pmid">29143192</pub-id></mixed-citation></ref><ref id="ref45"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ekiert</surname><given-names>D. C.</given-names></name><name><surname>Friesen</surname><given-names>R. H.</given-names></name><name><surname>Bhabha</surname><given-names>G.</given-names></name><name><surname>Kwaks</surname><given-names>T.</given-names></name><name><surname>Jongeneelen</surname><given-names>M.</given-names></name><name><surname>Yu</surname><given-names>W.</given-names></name><etal></etal></person-group>. (<year>2011</year>). <article-title>A highly conserved neutralizing epitope on group 2 influenza A viruses</article-title>. <source>Science</source><volume>333</volume>, <fpage>843</fpage>–<lpage>850</lpage>. <pub-id pub-id-type="doi">10.1126/science.1204839</pub-id>, PMID: <pub-id pub-id-type="pmid">21737702</pub-id></mixed-citation></ref><ref id="ref46"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Enjuanes</surname><given-names>L.</given-names></name><name><surname>Zuniga</surname><given-names>S.</given-names></name><name><surname>Castano-Rodriguez</surname><given-names>C.</given-names></name><name><surname>Gutierrez-Alvarez</surname><given-names>J.</given-names></name><name><surname>Canton</surname><given-names>J.</given-names></name><name><surname>Sola</surname><given-names>I.</given-names></name></person-group> (<year>2016</year>). <article-title>Molecular basis of coronavirus virulence and vaccine development</article-title>. <source>Adv. Virus Res.</source><volume>96</volume>, <fpage>245</fpage>–<lpage>286</lpage>. <pub-id pub-id-type="doi">10.1016/bs.aivir.2016.08.003</pub-id><pub-id pub-id-type="pmid">27712626</pub-id></mixed-citation></ref><ref id="ref47"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Erbelding</surname><given-names>E. J.</given-names></name><name><surname>Post</surname><given-names>D. J.</given-names></name><name><surname>Stemmy</surname><given-names>E. J.</given-names></name><name><surname>Roberts</surname><given-names>P. C.</given-names></name><name><surname>Augustine</surname><given-names>A. D.</given-names></name><name><surname>Ferguson</surname><given-names>S.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>A universal influenza vaccine: the strategic plan for the National Institute of Allergy and Infectious Diseases</article-title>. <source>J. Infect. Dis.</source><volume>218</volume>, <fpage>347</fpage>–<lpage>354</lpage>. <pub-id pub-id-type="doi">10.1093/infdis/jiy103</pub-id>, PMID: <pub-id pub-id-type="pmid">29506129</pub-id></mixed-citation></ref><ref id="ref48"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Falzarano</surname><given-names>D.</given-names></name><name><surname>De Wit</surname><given-names>E.</given-names></name><name><surname>Rasmussen</surname><given-names>A. L.</given-names></name><name><surname>Feldmann</surname><given-names>F.</given-names></name><name><surname>Okumura</surname><given-names>A.</given-names></name><name><surname>Scott</surname><given-names>D. P.</given-names></name><etal></etal></person-group>. (<year>2013</year>). <article-title>Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques</article-title>. <source>Nat. Med.</source><volume>19</volume>, <fpage>1313</fpage>–<lpage>1317</lpage>. <pub-id pub-id-type="doi">10.1038/nm.3362</pub-id>, PMID: <pub-id pub-id-type="pmid">24013700</pub-id></mixed-citation></ref><ref id="ref49"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ferkol</surname><given-names>T.</given-names></name><name><surname>Schraufnagel</surname><given-names>D.</given-names></name></person-group> (<year>2014</year>). <article-title>The global burden of respiratory disease</article-title>. <source>Ann. Am. Thorac. Soc.</source><volume>11</volume>, <fpage>404</fpage>–<lpage>406</lpage>. <pub-id pub-id-type="doi">10.1513/AnnalsATS.201311-405PS</pub-id><pub-id pub-id-type="pmid">24673696</pub-id></mixed-citation></ref><ref id="ref50"><mixed-citation publication-type="other"><person-group person-group-type="author"><collab id="coll5">Food and Drug Administration</collab></person-group> (<year>2018</year>). <article-title>FDA approves new drug to treat influenza</article-title>. <comment>Available at:</comment><ext-link ext-link-type="uri" xlink:href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624226.htm">https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm624226.htm</ext-link> (Accessed October 24, 2018).</mixed-citation></ref><ref id="ref51"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Friesen</surname><given-names>R. H.</given-names></name><name><surname>Koudstaal</surname><given-names>W.</given-names></name><name><surname>Koldijk</surname><given-names>M. H.</given-names></name><name><surname>Weverling</surname><given-names>G. J.</given-names></name><name><surname>Brakenhoff</surname><given-names>J. P.</given-names></name><name><surname>Lenting</surname><given-names>P. J.</given-names></name><etal></etal></person-group>. (<year>2010</year>). <article-title>New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets</article-title>. <source>PLoS One</source><volume>5</volume>:<fpage>e9106</fpage>. <pub-id pub-id-type="doi">10.1371/journal.pone.0009106</pub-id>, PMID: <pub-id pub-id-type="pmid">20161706</pub-id></mixed-citation></ref><ref id="ref52"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Frogel</surname><given-names>M.</given-names></name><name><surname>Nerwen</surname><given-names>C.</given-names></name><name><surname>Cohen</surname><given-names>A.</given-names></name><name><surname>Vanveldhuisen</surname><given-names>P.</given-names></name><name><surname>Harrington</surname><given-names>M.</given-names></name><name><surname>Boron</surname><given-names>M.</given-names></name></person-group> (<year>2008</year>). <article-title>Prevention of hospitalization due to respiratory syncytial virus: results from the palivizumab outcomes registry</article-title>. <source>J. Perinatol.</source><volume>28</volume>, <fpage>511</fpage>–<lpage>517</lpage>. <pub-id pub-id-type="doi">10.1038/jp.2008.28</pub-id>, PMID: <pub-id pub-id-type="pmid">18368063</pub-id></mixed-citation></ref><ref id="ref53"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fukao</surname><given-names>K.</given-names></name><name><surname>Noshi</surname><given-names>T.</given-names></name><name><surname>Yamamoto</surname><given-names>A.</given-names></name><name><surname>Kitano</surname><given-names>M.</given-names></name><name><surname>Ando</surname><given-names>Y.</given-names></name><name><surname>Noda</surname><given-names>T.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>Combination treatment with the cap-dependent endonuclease inhibitor baloxavir marboxil and a neuraminidase inhibitor in a mouse model of influenza A virus infection</article-title>. <source>J. Antimicrob. Chemother.</source><volume>74</volume>, <fpage>654</fpage>–<lpage>662</lpage>. <pub-id pub-id-type="doi">10.1093/jac/dky462</pub-id></mixed-citation></ref><ref id="ref54"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Furuta</surname><given-names>Y.</given-names></name><name><surname>Komeno</surname><given-names>T.</given-names></name><name><surname>Nakamura</surname><given-names>T.</given-names></name></person-group> (<year>2017</year>). <article-title>Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase</article-title>. <source>Proc. Jpn. Acad. Ser. B Phys. Biol. Sci.</source><volume>93</volume>, <fpage>449</fpage>–<lpage>463</lpage>. <pub-id pub-id-type="doi">10.2183/pjab.93.027</pub-id></mixed-citation></ref><ref id="ref55"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Furuta</surname><given-names>Y.</given-names></name><name><surname>Takahashi</surname><given-names>K.</given-names></name><name><surname>Kuno-Maekawa</surname><given-names>M.</given-names></name><name><surname>Sangawa</surname><given-names>H.</given-names></name><name><surname>Uehara</surname><given-names>S.</given-names></name><name><surname>Kozaki</surname><given-names>K.</given-names></name><etal></etal></person-group>. (<year>2005</year>). <article-title>Mechanism of action of T-705 against influenza virus</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>49</volume>, <fpage>981</fpage>–<lpage>986</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.49.3.981-986.2005</pub-id>, PMID: <pub-id pub-id-type="pmid">15728892</pub-id></mixed-citation></ref><ref id="ref56"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gottlieb</surname><given-names>J.</given-names></name><name><surname>Zamora</surname><given-names>M. R.</given-names></name><name><surname>Hodges</surname><given-names>T.</given-names></name><name><surname>Musk</surname><given-names>A.</given-names></name><name><surname>Sommerwerk</surname><given-names>U.</given-names></name><name><surname>Dilling</surname><given-names>D.</given-names></name><etal></etal></person-group>. (<year>2016</year>). <article-title>ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients</article-title>. <source>J. Heart Lung Transplant.</source><volume>35</volume>, <fpage>213</fpage>–<lpage>221</lpage>. <pub-id pub-id-type="doi">10.1016/j.healun.2015.08.012</pub-id>, PMID: <pub-id pub-id-type="pmid">26452996</pub-id></mixed-citation></ref><ref id="ref57"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Griffin</surname><given-names>M. P.</given-names></name><name><surname>Khan</surname><given-names>A. A.</given-names></name><name><surname>Esser</surname><given-names>M. T.</given-names></name><name><surname>Jensen</surname><given-names>K.</given-names></name><name><surname>Takas</surname><given-names>T.</given-names></name><name><surname>Kankam</surname><given-names>M. K.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>61</volume>, <fpage>e01714</fpage>–<lpage>e01716</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.01714-16</pub-id><pub-id pub-id-type="pmid">27956428</pub-id></mixed-citation></ref><ref id="ref58"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Griffiths</surname><given-names>C.</given-names></name><name><surname>Drews</surname><given-names>S. J.</given-names></name><name><surname>Marchant</surname><given-names>D. J.</given-names></name></person-group> (<year>2017</year>). <article-title>Respiratory syncytial virus: infection, detection, and new options for prevention and treatment</article-title>. <source>Clin. Microbiol. Rev.</source><volume>30</volume>, <fpage>277</fpage>–<lpage>319</lpage>. <pub-id pub-id-type="doi">10.1128/CMR.00010-16</pub-id><pub-id pub-id-type="pmid">27903593</pub-id></mixed-citation></ref><ref id="ref59"><mixed-citation publication-type="other"><person-group person-group-type="author"><name><surname>Gurnett-Bander</surname><given-names>A.</given-names></name><name><surname>Perez-Caballero</surname><given-names>D.</given-names></name><name><surname>Sivapalasingam</surname><given-names>S.</given-names></name><name><surname>Duan</surname><given-names>X.</given-names></name><name><surname>Macdonald</surname><given-names>D.</given-names></name></person-group> (<year>2016</year>). <article-title>Human antibodies to respiratory syncytial virus F protein and methods of use thereof</article-title>. <comment>Google Patents</comment>.</mixed-citation></ref><ref id="ref60"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Haffizulla</surname><given-names>J.</given-names></name><name><surname>Hartman</surname><given-names>A.</given-names></name><name><surname>Hoppers</surname><given-names>M.</given-names></name><name><surname>Resnick</surname><given-names>H.</given-names></name><name><surname>Samudrala</surname><given-names>S.</given-names></name><name><surname>Ginocchio</surname><given-names>C.</given-names></name><etal></etal></person-group>. (<year>2014</year>). <article-title>Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial</article-title>. <source>Lancet Infect. Dis.</source><volume>14</volume>, <fpage>609</fpage>–<lpage>618</lpage>. <pub-id pub-id-type="doi">10.1016/S1473-3099(14)70717-0</pub-id>, PMID: <pub-id pub-id-type="pmid">24852376</pub-id></mixed-citation></ref><ref id="ref61"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Hanfelt-Goade</surname><given-names>D.</given-names></name><name><surname>Maimon</surname><given-names>N.</given-names></name><name><surname>Nimer</surname><given-names>A.</given-names></name><name><surname>Riviere</surname><given-names>F.</given-names></name><name><surname>Catherinot</surname><given-names>E.</given-names></name><name><surname>Ison</surname><given-names>M.</given-names></name><etal></etal></person-group> (<year>2018</year>). “<article-title>A phase 2b, randomized, double-blind, placebo-controlled trial of Presatovir (GS-5806), a novel Oral RSV fusion inhibitor, for the treatment of respiratory syncytial virus (RSV) in hospitalized adults</article-title>” in <source>C17. New insights in acute pulmonary infections</source> (<publisher-loc>San Diego, CA</publisher-loc>: <publisher-name>American Thoracic Society</publisher-name>), <fpage>A4457</fpage>–<lpage>A4457</lpage>.</mixed-citation></ref><ref id="ref62"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hanton</surname><given-names>G.</given-names></name><name><surname>Detalle</surname><given-names>L.</given-names></name><name><surname>Priem</surname><given-names>S.</given-names></name><name><surname>Bouche</surname><given-names>M.-P.</given-names></name><name><surname>Depla</surname><given-names>E.</given-names></name><name><surname>Baumeister</surname><given-names>J.</given-names></name></person-group> (<year>2012</year>). <article-title>ALX-0171 toxicity study in RSV-infected cotton rats: safety and therapeutic potential</article-title>. <source>Toxicol. Lett.</source><volume>211</volume>:<fpage>S43</fpage>. <pub-id pub-id-type="doi">10.1016/j.toxlet.2012.03.176</pub-id></mixed-citation></ref><ref id="ref63"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hayden</surname><given-names>F. G.</given-names></name><name><surname>Sugaya</surname><given-names>N.</given-names></name><name><surname>Hirotsu</surname><given-names>N.</given-names></name><name><surname>Lee</surname><given-names>N.</given-names></name><name><surname>De Jong</surname><given-names>M. D.</given-names></name><name><surname>Hurt</surname><given-names>A. C.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Baloxavir Marboxil for uncomplicated influenza in adults and adolescents</article-title>. <source>N. Engl. J. Med.</source><volume>379</volume>, <fpage>913</fpage>–<lpage>923</lpage>. <pub-id pub-id-type="doi">10.1056/NEJMoa1716197</pub-id>, PMID: <pub-id pub-id-type="pmid">30184455</pub-id></mixed-citation></ref><ref id="ref64"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Haynes</surname><given-names>L. M.</given-names></name><name><surname>Caidi</surname><given-names>H.</given-names></name><name><surname>Radu</surname><given-names>G. U.</given-names></name><name><surname>Miao</surname><given-names>C.</given-names></name><name><surname>Harcourt</surname><given-names>J. L.</given-names></name><name><surname>Tripp</surname><given-names>R. A.</given-names></name><etal></etal></person-group>. (<year>2009</year>). <article-title>Therapeutic monoclonal antibody treatment targeting respiratory syncytial virus (RSV) G protein mediates viral clearance and reduces the pathogenesis of RSV infection in BALB/c mice</article-title>. <source>J. Infect. Dis.</source><volume>200</volume>, <fpage>439</fpage>–<lpage>447</lpage>. <pub-id pub-id-type="doi">10.1086/600108</pub-id>, PMID: <pub-id pub-id-type="pmid">19545210</pub-id></mixed-citation></ref><ref id="ref65"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Heylen</surname><given-names>E.</given-names></name><name><surname>Neyts</surname><given-names>J.</given-names></name><name><surname>Jochmans</surname><given-names>D.</given-names></name></person-group> (<year>2017</year>). <article-title>Drug candidates and model systems in respiratory syncytial virus antiviral drug discovery</article-title>. <source>Biochem. Pharmacol.</source><volume>127</volume>, <fpage>1</fpage>–<lpage>12</lpage>. <pub-id pub-id-type="doi">10.1016/j.bcp.2016.09.014</pub-id>, PMID: <pub-id pub-id-type="pmid">27659812</pub-id></mixed-citation></ref><ref id="ref66"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hotard</surname><given-names>A. L.</given-names></name><name><surname>Lee</surname><given-names>S.</given-names></name><name><surname>Currier</surname><given-names>M. G.</given-names></name><name><surname>Crowe</surname><given-names>J. E.</given-names></name><name><surname>Sakamoto</surname><given-names>K.</given-names></name><name><surname>Newcomb</surname><given-names>D. C.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Identification of residues in the human respiratory syncytial virus fusion protein that modulate fusion activity and pathogenesis</article-title>. <source>J. Virol.</source><volume>89</volume>, <fpage>512</fpage>–<lpage>522</lpage>. <pub-id pub-id-type="doi">10.1128/JVI.02472-14</pub-id><pub-id pub-id-type="pmid">25339762</pub-id></mixed-citation></ref><ref id="ref67"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huntjens</surname><given-names>D. R.</given-names></name><name><surname>Ouwerkerk-Mahadevan</surname><given-names>S.</given-names></name><name><surname>Brochot</surname><given-names>A.</given-names></name><name><surname>Rusch</surname><given-names>S.</given-names></name><name><surname>Stevens</surname><given-names>M.</given-names></name><name><surname>Verloes</surname><given-names>R.</given-names></name></person-group> (<year>2017</year>). <article-title>Population pharmacokinetic modeling of JNJ-53718678, a novel fusion inhibitor for the treatment of respiratory syncytial virus: results from a phase I, double-blind, randomized, placebo-controlled first-in-human study in healthy adult subjects</article-title>. <source>Clin. Pharmacokinet.</source><volume>56</volume>, <fpage>1331</fpage>–<lpage>1342</lpage>. <pub-id pub-id-type="doi">10.1007/s40262-017-0522-8</pub-id>, PMID: <pub-id pub-id-type="pmid">28238203</pub-id></mixed-citation></ref><ref id="ref68"><mixed-citation publication-type="journal"><person-group person-group-type="author"><collab id="coll6">International Society for Influenza and other Respiratory Viral Diseases</collab></person-group> (<year>2018</year>). <article-title>Prevention and treatment of respiratory viral infections: presentations on antiviral, traditional therapies and host-directed interventions at the 5th ISIRV antiviral group conference. Meeting report</article-title>. <source>Antiviral Res.</source><volume>149</volume>, <fpage>118</fpage>–<lpage>142</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2017.11.013</pub-id>, PMID: <pub-id pub-id-type="pmid">29162476</pub-id></mixed-citation></ref><ref id="ref69"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ison</surname><given-names>M. G.</given-names></name></person-group> (<year>2017</year>). <article-title>Antiviral treatments</article-title>. <source>Clin. Chest Med.</source><volume>38</volume>, <fpage>139</fpage>–<lpage>153</lpage>. <pub-id pub-id-type="doi">10.1016/j.ccm.2016.11.008</pub-id>, PMID: <pub-id pub-id-type="pmid">28159156</pub-id></mixed-citation></ref><ref id="ref70"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ispas</surname><given-names>G.</given-names></name><name><surname>Koul</surname><given-names>A.</given-names></name><name><surname>Verbeeck</surname><given-names>J.</given-names></name><name><surname>Sheehan</surname><given-names>J.</given-names></name><name><surname>Sanders-Beer</surname><given-names>B.</given-names></name><name><surname>Roymans</surname><given-names>D.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Antiviral activity of TMC353121, a respiratory syncytial virus (RSV) fusion inhibitor, in a non-human primate model</article-title>. <source>PLoS One</source><volume>10</volume>:<fpage>e0126959</fpage>. <pub-id pub-id-type="doi">10.1371/journal.pone.0126959</pub-id>, PMID: <pub-id pub-id-type="pmid">26010881</pub-id></mixed-citation></ref><ref id="ref71"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Israel</surname><given-names>S.</given-names></name><name><surname>Rusch</surname><given-names>S.</given-names></name><name><surname>Devincenzo</surname><given-names>J.</given-names></name><name><surname>Boyers</surname><given-names>A.</given-names></name><name><surname>Fok-Seang</surname><given-names>J.</given-names></name><name><surname>Huntjens</surname><given-names>D.</given-names></name><etal></etal></person-group> (<year>2016</year>). “<article-title>Effect of oral JNJ-53718678 (JNJ-678) on disease severity in healthy adult volunteers experimentally inoculated with live respiratory syncytial virus (RSV): a placebo-controlled challenge study</article-title>” in <source>Open forum infectious diseases</source> (<publisher-loc>New Orleans, LA</publisher-loc>: <publisher-name>Oxford University Press</publisher-name>).</mixed-citation></ref><ref id="ref72"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jin</surname><given-names>Y.</given-names></name><name><surname>Lei</surname><given-names>C.</given-names></name><name><surname>Hu</surname><given-names>D.</given-names></name><name><surname>Dimitrov</surname><given-names>D. S.</given-names></name><name><surname>Ying</surname><given-names>T.</given-names></name></person-group> (<year>2017</year>). <article-title>Human monoclonal antibodies as candidate therapeutics against emerging viruses</article-title>. <source>Front. Med.</source><volume>11</volume>, <fpage>462</fpage>–<lpage>470</lpage>. <pub-id pub-id-type="doi">10.1007/s11684-017-0596-6</pub-id>, PMID: <pub-id pub-id-type="pmid">29159596</pub-id></mixed-citation></ref><ref id="ref73"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johnson</surname><given-names>S. M.</given-names></name><name><surname>McNally</surname><given-names>B. A.</given-names></name><name><surname>Ioannidis</surname><given-names>I.</given-names></name><name><surname>Flano</surname><given-names>E.</given-names></name><name><surname>Teng</surname><given-names>M. N.</given-names></name><name><surname>Oomens</surname><given-names>A. G.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Respiratory syncytial virus uses CX3CR1 as a receptor on primary human airway epithelial cultures</article-title>. <source>PLoS Pathog.</source><volume>11</volume>:<fpage>e1005318</fpage>. <pub-id pub-id-type="doi">10.1371/journal.ppat.1005318</pub-id>, PMID: <pub-id pub-id-type="pmid">26658574</pub-id></mixed-citation></ref><ref id="ref74"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jones</surname><given-names>J. C.</given-names></name><name><surname>Kumar</surname><given-names>G.</given-names></name><name><surname>Barman</surname><given-names>S.</given-names></name><name><surname>Najera</surname><given-names>I.</given-names></name><name><surname>White</surname><given-names>S. W.</given-names></name><name><surname>Webby</surname><given-names>R. J.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Identification of the I38T PA substitution as a resistance marker for next-generation influenza virus endonuclease inhibitors</article-title>. <source>MBio</source><volume>9</volume>:<fpage>e00430-18</fpage>. <pub-id pub-id-type="doi">10.1128/mBio.01868-18</pub-id>, PMID: <pub-id pub-id-type="pmid">29691337</pub-id></mixed-citation></ref><ref id="ref75"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jordan</surname><given-names>P. C.</given-names></name><name><surname>Stevens</surname><given-names>S. K.</given-names></name><name><surname>Deval</surname><given-names>J.</given-names></name></person-group> (<year>2018</year>). <article-title>Nucleosides for the treatment of respiratory RNA virus infections</article-title>. <source>Antivir. Chem. Chemother.</source><volume>26</volume>:<fpage>2040206618764483</fpage>. <pub-id pub-id-type="doi">10.1177/2040206618764483</pub-id>, PMID: <pub-id pub-id-type="pmid">29562753</pub-id></mixed-citation></ref><ref id="ref76"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jorquera</surname><given-names>P. A.</given-names></name><name><surname>Tripp</surname><given-names>R. A.</given-names></name></person-group> (<year>2017</year>). <article-title>Respiratory syncytial virus: prospects for new and emerging therapeutics</article-title>. <source>Expert Rev. Respir. Med.</source><volume>11</volume>, <fpage>609</fpage>–<lpage>615</lpage>. <pub-id pub-id-type="doi">10.1080/17476348.2017.1338567</pub-id>, PMID: <pub-id pub-id-type="pmid">28574729</pub-id></mixed-citation></ref><ref id="ref77"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kallewaard</surname><given-names>N. L.</given-names></name><name><surname>Corti</surname><given-names>D.</given-names></name><name><surname>Collins</surname><given-names>P. J.</given-names></name><name><surname>Neu</surname><given-names>U.</given-names></name><name><surname>McAuliffe</surname><given-names>J. M.</given-names></name><name><surname>Benjamin</surname><given-names>E.</given-names></name><etal></etal></person-group>. (<year>2016</year>). <article-title>Structure and function analysis of an antibody recognizing all influenza A subtypes</article-title>. <source>Cell</source><volume>166</volume>, <fpage>596</fpage>–<lpage>608</lpage>. <pub-id pub-id-type="doi">10.1016/j.cell.2016.05.073</pub-id>, PMID: <pub-id pub-id-type="pmid">27453466</pub-id></mixed-citation></ref><ref id="ref78"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kapoor</surname><given-names>M.</given-names></name><name><surname>Pringle</surname><given-names>K.</given-names></name><name><surname>Kumar</surname><given-names>A.</given-names></name><name><surname>Dearth</surname><given-names>S.</given-names></name><name><surname>Liu</surname><given-names>L.</given-names></name><name><surname>Lovchik</surname><given-names>J.</given-names></name><etal></etal></person-group>. (<year>2014</year>). <article-title>Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States</article-title>. <source>Clin. Infect. Dis.</source><volume>59</volume>, <fpage>1511</fpage>–<lpage>1518</lpage>. <pub-id pub-id-type="doi">10.1093/cid/ciu635</pub-id>, PMID: <pub-id pub-id-type="pmid">25100864</pub-id></mixed-citation></ref><ref id="ref79"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Khalid</surname><given-names>M.</given-names></name><name><surname>Al Rabiah</surname><given-names>F.</given-names></name><name><surname>Khan</surname><given-names>B.</given-names></name><name><surname>Al Mobeireek</surname><given-names>A.</given-names></name><name><surname>Butt</surname><given-names>T. S.</given-names></name><name><surname>Al Mutairy</surname><given-names>E.</given-names></name></person-group> (<year>2015</year>). <article-title>Ribavirin and interferon-alpha2b as primary and preventive treatment for Middle East respiratory syndrome coronavirus: a preliminary report of two cases</article-title>. <source>Antivir. Ther.</source><volume>20</volume>, <fpage>87</fpage>–<lpage>91</lpage>. <pub-id pub-id-type="doi">10.3851/IMP2792</pub-id>, PMID: <pub-id pub-id-type="pmid">24831606</pub-id></mixed-citation></ref><ref id="ref80"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ki</surname><given-names>M.</given-names></name></person-group> (<year>2015</year>). <article-title>2015 MERS outbreak in Korea: hospital-to-hospital transmission</article-title>. <source>Epidemiol. Health</source><volume>37</volume>:<fpage>e2015033</fpage>. <pub-id pub-id-type="doi">10.4178/epih/e2015033</pub-id>, PMID: <pub-id pub-id-type="pmid">26212508</pub-id></mixed-citation></ref><ref id="ref81"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>Y. I.</given-names></name><name><surname>Pareek</surname><given-names>R.</given-names></name><name><surname>Murphy</surname><given-names>R.</given-names></name><name><surname>Harrison</surname><given-names>L.</given-names></name><name><surname>Farrell</surname><given-names>E.</given-names></name><name><surname>Cook</surname><given-names>R.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>The antiviral effects of RSV fusion inhibitor, MDT-637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin</article-title>. <source>Influenza Other Respir. Viruses</source><volume>11</volume>, <fpage>525</fpage>–<lpage>530</lpage>. <pub-id pub-id-type="doi">10.1111/irv.12503</pub-id><pub-id pub-id-type="pmid">28990339</pub-id></mixed-citation></ref><ref id="ref82"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>J.</given-names></name><name><surname>Seong</surname><given-names>R.-K.</given-names></name><name><surname>Kumar</surname><given-names>M.</given-names></name><name><surname>Shin</surname><given-names>O. S.</given-names></name></person-group> (<year>2018</year>). <article-title>Favipiravir and ribavirin inhibit replication of Asian and African strains of Zika virus in different cell models</article-title>. <source>Viruses</source><volume>10</volume>:<fpage>72</fpage>. <pub-id pub-id-type="doi">10.3390/v10020072</pub-id>, PMID: <pub-id pub-id-type="pmid">29425176</pub-id></mixed-citation></ref><ref id="ref83"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>U. J.</given-names></name><name><surname>Won</surname><given-names>E. J.</given-names></name><name><surname>Kee</surname><given-names>S. J.</given-names></name><name><surname>Jung</surname><given-names>S. I.</given-names></name><name><surname>Jang</surname><given-names>H. C.</given-names></name></person-group> (<year>2016</year>). <article-title>Combination therapy with lopinavir/ritonavir, ribavirin and interferon-alpha for Middle East respiratory syndrome</article-title>. <source>Antivir. Ther.</source><volume>21</volume>, <fpage>455</fpage>–<lpage>459</lpage>. <pub-id pub-id-type="doi">10.3851/IMP3002</pub-id>, PMID: <pub-id pub-id-type="pmid">26492219</pub-id></mixed-citation></ref><ref id="ref84"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Koszalka</surname><given-names>P.</given-names></name><name><surname>Tilmanis</surname><given-names>D.</given-names></name><name><surname>Hurt</surname><given-names>A. C.</given-names></name></person-group> (<year>2017</year>). <article-title>Influenza antivirals currently in late-phase clinical trial</article-title>. <source>Influenza Other Respir. Viruses</source><volume>11</volume>, <fpage>240</fpage>–<lpage>246</lpage>. <pub-id pub-id-type="doi">10.1111/irv.12446</pub-id>, PMID: <pub-id pub-id-type="pmid">28146320</pub-id></mixed-citation></ref><ref id="ref85"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Koudstaal</surname><given-names>W.</given-names></name><name><surname>Koldijk</surname><given-names>M. H.</given-names></name><name><surname>Brakenhoff</surname><given-names>J. P.</given-names></name><name><surname>Cornelissen</surname><given-names>L. A.</given-names></name><name><surname>Weverling</surname><given-names>G. J.</given-names></name><name><surname>Friesen</surname><given-names>R. H.</given-names></name><etal></etal></person-group>. (<year>2009</year>). <article-title>Pre- and postexposure use of human monoclonal antibody against H5N1 and H1N1 influenza virus in mice: viable alternative to oseltamivir</article-title>. <source>J. Infect. Dis.</source><volume>200</volume>, <fpage>1870</fpage>–<lpage>1873</lpage>. <pub-id pub-id-type="doi">10.1086/648378</pub-id>, PMID: <pub-id pub-id-type="pmid">19911992</pub-id></mixed-citation></ref><ref id="ref86"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lim</surname><given-names>J. J.</given-names></name><name><surname>Deng</surname><given-names>R.</given-names></name><name><surname>Derby</surname><given-names>M. A.</given-names></name><name><surname>Larouche</surname><given-names>R.</given-names></name><name><surname>Horn</surname><given-names>P.</given-names></name><name><surname>Anderson</surname><given-names>M.</given-names></name><etal></etal></person-group>. (<year>2016</year>). <article-title>Two phase 1, randomized, double-blind, placebo-controlled, single-ascending-dose studies to investigate the safety, tolerability, and pharmacokinetics of an anti-influenza A virus monoclonal antibody, MHAA4549A, in healthy volunteers</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>60</volume>, <fpage>5437</fpage>–<lpage>5444</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.00607-16</pub-id>, PMID: <pub-id pub-id-type="pmid">27381392</pub-id></mixed-citation></ref><ref id="ref87"><mixed-citation publication-type="other"><person-group person-group-type="author"><name><surname>Lu</surname><given-names>P. Y.</given-names></name><name><surname>Evans</surname><given-names>D. M.</given-names></name><name><surname>Xu</surname><given-names>J. J.</given-names></name><name><surname>Lu</surname><given-names>A. Y.</given-names></name><name><surname>Ge</surname><given-names>Q.</given-names></name></person-group> (<year>2018</year>). <article-title>Compositions and methods for “resistance-proof” SiRNA therapeutics for influenza</article-title>. <comment>Google Patents</comment>.</mixed-citation></ref><ref id="ref88"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Luke</surname><given-names>T.</given-names></name><name><surname>Wu</surname><given-names>H.</given-names></name><name><surname>Zhao</surname><given-names>J.</given-names></name><name><surname>Channappanavar</surname><given-names>R.</given-names></name><name><surname>Coleman</surname><given-names>C. M.</given-names></name><name><surname>Jiao</surname><given-names>J. A.</given-names></name><etal></etal></person-group>. (<year>2016</year>). <article-title>Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo</article-title>. <source>Sci. Transl. Med.</source><volume>8</volume>:<fpage>326ra321</fpage>. <pub-id pub-id-type="doi">10.1126/scitranslmed.aaf1061</pub-id>, PMID: <pub-id pub-id-type="pmid">26888429</pub-id></mixed-citation></ref><ref id="ref89"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mackman</surname><given-names>R. L.</given-names></name><name><surname>Sangi</surname><given-names>M.</given-names></name><name><surname>Sperandio</surname><given-names>D.</given-names></name><name><surname>Parrish</surname><given-names>J. P.</given-names></name><name><surname>Eisenberg</surname><given-names>E.</given-names></name><name><surname>Perron</surname><given-names>M.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study</article-title>. <source>J. Med. Chem.</source><volume>58</volume>, <fpage>1630</fpage>–<lpage>1643</lpage>. <pub-id pub-id-type="doi">10.1021/jm5017768</pub-id><pub-id pub-id-type="pmid">25574686</pub-id></mixed-citation></ref><ref id="ref90"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mair-Jenkins</surname><given-names>J.</given-names></name><name><surname>Saavedra-Campos</surname><given-names>M.</given-names></name><name><surname>Baillie</surname><given-names>J. K.</given-names></name><name><surname>Cleary</surname><given-names>P.</given-names></name><name><surname>Khaw</surname><given-names>F. M.</given-names></name><name><surname>Lim</surname><given-names>W. S.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis</article-title>. <source>J. Infect. Dis.</source><volume>211</volume>, <fpage>80</fpage>–<lpage>90</lpage>. <pub-id pub-id-type="doi">10.1093/infdis/jiu396</pub-id><pub-id pub-id-type="pmid">25030060</pub-id></mixed-citation></ref><ref id="ref91"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malakhov</surname><given-names>M. P.</given-names></name><name><surname>Aschenbrenner</surname><given-names>L. M.</given-names></name><name><surname>Smee</surname><given-names>D. F.</given-names></name><name><surname>Wandersee</surname><given-names>M. K.</given-names></name><name><surname>Sidwell</surname><given-names>R. W.</given-names></name><name><surname>Gubareva</surname><given-names>L. V.</given-names></name><etal></etal></person-group>. (<year>2006</year>). <article-title>Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>50</volume>, <fpage>1470</fpage>–<lpage>1479</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.50.4.1470-1479.2006</pub-id>, PMID: <pub-id pub-id-type="pmid">16569867</pub-id></mixed-citation></ref><ref id="ref92"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marjuki</surname><given-names>H.</given-names></name><name><surname>Mishin</surname><given-names>V. P.</given-names></name><name><surname>Chesnokov</surname><given-names>A. P.</given-names></name><name><surname>De La Cruz</surname><given-names>J. A.</given-names></name><name><surname>Fry</surname><given-names>A. M.</given-names></name><name><surname>Villanueva</surname><given-names>J.</given-names></name><etal></etal></person-group>. (<year>2014</year>). <article-title>An investigational antiviral drug, DAS181, effectively inhibits replication of zoonotic influenza A virus subtype H7N9 and protects mice from lethality</article-title>. <source>J. Infect. Dis.</source><volume>210</volume>, <fpage>435</fpage>–<lpage>440</lpage>. <pub-id pub-id-type="doi">10.1093/infdis/jiu105</pub-id>, PMID: <pub-id pub-id-type="pmid">24569063</pub-id></mixed-citation></ref><ref id="ref93"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marjuki</surname><given-names>H.</given-names></name><name><surname>Mishin</surname><given-names>V. P.</given-names></name><name><surname>Chesnokov</surname><given-names>A. P.</given-names></name><name><surname>Jones</surname><given-names>J.</given-names></name><name><surname>De La Cruz</surname><given-names>J. A.</given-names></name><name><surname>Sleeman</surname><given-names>K.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Characterization of drug-resistant influenza A(H7N9) variants isolated from an oseltamivir-treated patient in Taiwan</article-title>. <source>J. Infect. Dis.</source><volume>211</volume>, <fpage>249</fpage>–<lpage>257</lpage>. <pub-id pub-id-type="doi">10.1093/infdis/jiu447</pub-id><pub-id pub-id-type="pmid">25124927</pub-id></mixed-citation></ref><ref id="ref94"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Marty</surname><given-names>F.</given-names></name><name><surname>Chemaly</surname><given-names>R.</given-names></name><name><surname>Liakopoulou</surname><given-names>E.</given-names></name><name><surname>Dent</surname><given-names>J.</given-names></name><name><surname>Powell</surname><given-names>K.</given-names></name></person-group> (<year>2007</year>). “<article-title>A double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of RSV604 in adults with respiratory syncytial virus infection following stem cell transplantation</article-title>” in <source>Proceedings of the IXth international symposium on respiratory viral infections.</source><publisher-name>International Society for Influenza and other Respiratory Virus Diseases (ISIRV)</publisher-name>.</mixed-citation></ref><ref id="ref95"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsushita</surname><given-names>H.</given-names></name><name><surname>Sano</surname><given-names>A.</given-names></name><name><surname>Wu</surname><given-names>H.</given-names></name><name><surname>Jiao</surname><given-names>J. A.</given-names></name><name><surname>Kasinathan</surname><given-names>P.</given-names></name><name><surname>Sullivan</surname><given-names>E. J.</given-names></name><etal></etal></person-group>. (<year>2014</year>). <article-title>Triple immunoglobulin gene knockout transchromosomic cattle: bovine lambda cluster deletion and its effect on fully human polyclonal antibody production</article-title>. <source>PLoS One</source><volume>9</volume>:<fpage>e90383</fpage>. <pub-id pub-id-type="doi">10.1371/journal.pone.0090383</pub-id>, PMID: <pub-id pub-id-type="pmid">24603704</pub-id></mixed-citation></ref><ref id="ref96"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McBride</surname><given-names>J. M.</given-names></name><name><surname>Lim</surname><given-names>J. J.</given-names></name><name><surname>Burgess</surname><given-names>T.</given-names></name><name><surname>Deng</surname><given-names>R.</given-names></name><name><surname>Derby</surname><given-names>M. A.</given-names></name><name><surname>Maia</surname><given-names>M.</given-names></name><etal></etal></person-group>. (<year>2017</year>). <article-title>Phase 2 randomized trial of the safety and efficacy of MHAA4549A, a broadly neutralizing monoclonal antibody, in a human influenza A virus challenge model</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>61</volume>:<fpage>e01154-17</fpage>. <pub-id pub-id-type="doi">10.1128/AAC.01154-17</pub-id>, PMID: <pub-id pub-id-type="pmid">28807912</pub-id></mixed-citation></ref><ref id="ref97"><mixed-citation publication-type="other"><person-group person-group-type="author"><name><surname>McIntosh</surname><given-names>K.</given-names></name></person-group> (<year>2017</year>). <article-title>Middle east respiratory syndrome coronavirus: Treatment and prevention</article-title>.</mixed-citation></ref><ref id="ref98"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Memish</surname><given-names>Z. A.</given-names></name><name><surname>Zumla</surname><given-names>A. I.</given-names></name><name><surname>Assiri</surname><given-names>A.</given-names></name></person-group> (<year>2013</year>). <article-title>Middle East respiratory syndrome coronavirus infections in health care workers</article-title>. <source>N. Engl. J. Med.</source><volume>369</volume>, <fpage>884</fpage>–<lpage>886</lpage>. <pub-id pub-id-type="doi">10.1056/NEJMc1308698</pub-id>, PMID: <pub-id pub-id-type="pmid">23923992</pub-id></mixed-citation></ref><ref id="ref99"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mo</surname><given-names>Y.</given-names></name><name><surname>Fisher</surname><given-names>D.</given-names></name></person-group> (<year>2016</year>). <article-title>A review of treatment modalities for Middle East respiratory syndrome</article-title>. <source>J. Antimicrob. Chemother.</source><volume>71</volume>, <fpage>3340</fpage>–<lpage>3350</lpage>. <pub-id pub-id-type="doi">10.1093/jac/dkw338</pub-id>, PMID: <pub-id pub-id-type="pmid">27585965</pub-id></mixed-citation></ref><ref id="ref100"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Modjarrad</surname><given-names>K.</given-names></name></person-group> (<year>2016</year>). <article-title>Treatment strategies for Middle East respiratory syndrome coronavirus</article-title>. <source>J. Virus Erad.</source><volume>2</volume>, <fpage>1</fpage>–<lpage>4</lpage>. PMID: <pub-id pub-id-type="pmid">26866060</pub-id></mixed-citation></ref><ref id="ref101"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Momattin</surname><given-names>H.</given-names></name><name><surname>Mohammed</surname><given-names>K.</given-names></name><name><surname>Zumla</surname><given-names>A.</given-names></name><name><surname>Memish</surname><given-names>Z. A.</given-names></name><name><surname>Al-Tawfiq</surname><given-names>J. A.</given-names></name></person-group> (<year>2013</year>). <article-title>Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV) – possible lessons from a systematic review of SARS-CoV therapy</article-title>. <source>Int. J. Infect. Dis.</source><volume>17</volume>, <fpage>e792</fpage>–<lpage>e798</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijid.2013.07.002</pub-id>, PMID: <pub-id pub-id-type="pmid">23993766</pub-id></mixed-citation></ref><ref id="ref102"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Morris</surname><given-names>J.</given-names></name><name><surname>Blount</surname><given-names>R.</given-names><suffix>Jr.</suffix></name><name><surname>Savage</surname><given-names>R.</given-names></name></person-group> (<year>1956</year>). <article-title>Recovery of cytopathogenic agent from chimpanzees with goryza</article-title>. <source>Proc. Soc. Exp. Biol. Med.</source><volume>92</volume>, <fpage>544</fpage>–<lpage>549</lpage>.<pub-id pub-id-type="pmid">13359460</pub-id></mixed-citation></ref><ref id="ref103"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moss</surname><given-names>R. B.</given-names></name><name><surname>Hansen</surname><given-names>C.</given-names></name><name><surname>Sanders</surname><given-names>R. L.</given-names></name><name><surname>Hawley</surname><given-names>S.</given-names></name><name><surname>Li</surname><given-names>T.</given-names></name><name><surname>Steigbigel</surname><given-names>R. T.</given-names></name></person-group> (<year>2012</year>). <article-title>A phase II study of DAS181, a novel host directed antiviral for the treatment of influenza infection</article-title>. <source>J. Infect. Dis.</source><volume>206</volume>, <fpage>1844</fpage>–<lpage>1851</lpage>. <pub-id pub-id-type="doi">10.1093/infdis/jis622</pub-id>, PMID: <pub-id pub-id-type="pmid">23045618</pub-id></mixed-citation></ref><ref id="ref104"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mustafa</surname><given-names>S.</given-names></name><name><surname>Balkhy</surname><given-names>H.</given-names></name><name><surname>Gabere</surname><given-names>M. N.</given-names></name></person-group> (<year>2018</year>). <article-title>Current treatment options and the role of peptides as potential therapeutic components for Middle East respiratory syndrome (MERS): a review</article-title>. <source>J. Infect. Public Health</source><volume>11</volume>, <fpage>9</fpage>–<lpage>17</lpage>. <pub-id pub-id-type="doi">10.1016/j.jiph.2017.08.009</pub-id>, PMID: <pub-id pub-id-type="pmid">28864360</pub-id></mixed-citation></ref><ref id="ref105"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nakamura</surname><given-names>G.</given-names></name><name><surname>Chai</surname><given-names>N.</given-names></name><name><surname>Park</surname><given-names>S.</given-names></name><name><surname>Chiang</surname><given-names>N.</given-names></name><name><surname>Lin</surname><given-names>Z.</given-names></name><name><surname>Chiu</surname><given-names>H.</given-names></name><etal></etal></person-group>. (<year>2013</year>). <article-title>An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza A antibodies</article-title>. <source>Cell Host Microbe</source><volume>14</volume>, <fpage>93</fpage>–<lpage>103</lpage>. <pub-id pub-id-type="doi">10.1016/j.chom.2013.06.004</pub-id>, PMID: <pub-id pub-id-type="pmid">23870317</pub-id></mixed-citation></ref><ref id="ref106"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Noshi</surname><given-names>T.</given-names></name><name><surname>Kitano</surname><given-names>M.</given-names></name><name><surname>Taniguchi</surname><given-names>K.</given-names></name><name><surname>Yamamoto</surname><given-names>A.</given-names></name><name><surname>Omoto</surname><given-names>S.</given-names></name><name><surname>Baba</surname><given-names>K.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit</article-title>. <source>Antiviral Res.</source><volume>160</volume>, <fpage>109</fpage>–<lpage>117</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2018.10.008</pub-id><pub-id pub-id-type="pmid">30316915</pub-id></mixed-citation></ref><ref id="ref107"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>O’brien</surname><given-names>K. L.</given-names></name><name><surname>Chandran</surname><given-names>A.</given-names></name><name><surname>Weatherholtz</surname><given-names>R.</given-names></name><name><surname>Jafri</surname><given-names>H. S.</given-names></name><name><surname>Griffin</surname><given-names>M. P.</given-names></name><name><surname>Bellamy</surname><given-names>T.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Efficacy of motavizumab for the prevention of respiratory syncytial virus disease in healthy native American infants: a phase 3 randomised double-blind placebo-controlled trial</article-title>. <source>Lancet Infect. Dis.</source><volume>15</volume>, <fpage>1398</fpage>–<lpage>1408</lpage>. <pub-id pub-id-type="doi">10.1016/S1473-3099(15)00247-9</pub-id>, PMID: <pub-id pub-id-type="pmid">26511956</pub-id></mixed-citation></ref><ref id="ref108"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Omrani</surname><given-names>A. S.</given-names></name><name><surname>Shalhoub</surname><given-names>S.</given-names></name></person-group> (<year>2015</year>). <article-title>Middle East respiratory syndrome coronavirus (MERS-CoV): what lessons can we learn?</article-title><source>J. Hosp. Infect.</source><volume>91</volume>, <fpage>188</fpage>–<lpage>196</lpage>. <pub-id pub-id-type="doi">10.1016/j.jhin.2015.08.002</pub-id>, PMID: <pub-id pub-id-type="pmid">26452615</pub-id></mixed-citation></ref><ref id="ref109"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ormond</surname><given-names>L.</given-names></name><name><surname>Liu</surname><given-names>P.</given-names></name><name><surname>Matuszewski</surname><given-names>S.</given-names></name><name><surname>Renzette</surname><given-names>N.</given-names></name><name><surname>Bank</surname><given-names>C.</given-names></name><name><surname>Zeldovich</surname><given-names>K.</given-names></name><etal></etal></person-group>. (<year>2017</year>). <article-title>The combined effect of oseltamivir and favipiravir on influenza A virus evolution</article-title>. <source>Genome Biol. Evol.</source><volume>9</volume>, <fpage>1913</fpage>–<lpage>1924</lpage>. <pub-id pub-id-type="doi">10.1093/gbe/evx138</pub-id>, PMID: <pub-id pub-id-type="pmid">28854600</pub-id></mixed-citation></ref><ref id="ref110"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paden</surname><given-names>C. R.</given-names></name><name><surname>Yusof</surname><given-names>M.</given-names></name><name><surname>Al Hammadi</surname><given-names>Z. M.</given-names></name><name><surname>Queen</surname><given-names>K.</given-names></name><name><surname>Tao</surname><given-names>Y.</given-names></name><name><surname>Eltahir</surname><given-names>Y. M.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Zoonotic origin and transmission of Middle East respiratory syndrome coronavirus in the UAE</article-title>. <source>Zoonoses Public Health</source><volume>65</volume>, <fpage>322</fpage>–<lpage>333</lpage>. <pub-id pub-id-type="doi">10.1111/zph.12435</pub-id>, PMID: <pub-id pub-id-type="pmid">29239118</pub-id></mixed-citation></ref><ref id="ref111"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Palese</surname><given-names>P.</given-names></name><name><surname>Bodo</surname><given-names>G.</given-names></name><name><surname>Tuppy</surname><given-names>H.</given-names></name></person-group> (<year>1970</year>). <article-title>Quantitative determination of neuraminidase-active foci in cell monolayer cultures infected with influenza or Newcastle disease virus</article-title>. <source>J. Virol.</source><volume>6</volume>, <fpage>556</fpage>–<lpage>558</lpage>. PMID: <pub-id pub-id-type="pmid">5497902</pub-id></mixed-citation></ref><ref id="ref112"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Park</surname><given-names>S. Y.</given-names></name><name><surname>Lee</surname><given-names>J. S.</given-names></name><name><surname>Son</surname><given-names>J. S.</given-names></name><name><surname>Ko</surname><given-names>J. H.</given-names></name><name><surname>Peck</surname><given-names>K. R.</given-names></name><name><surname>Jung</surname><given-names>Y.</given-names></name><etal></etal></person-group>. (<year>2019</year>). <article-title>Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers</article-title>. <source>J. Hosp. Infect.</source><volume>101</volume>, <fpage>42</fpage>–<lpage>46</lpage>. <pub-id pub-id-type="doi">10.1016/j.jhin.2018.09.005</pub-id>, PMID: <pub-id pub-id-type="pmid">30240813</pub-id></mixed-citation></ref><ref id="ref113"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pascal</surname><given-names>K. E.</given-names></name><name><surname>Coleman</surname><given-names>C. M.</given-names></name><name><surname>Mujica</surname><given-names>A. O.</given-names></name><name><surname>Kamat</surname><given-names>V.</given-names></name><name><surname>Badithe</surname><given-names>A.</given-names></name><name><surname>Fairhurst</surname><given-names>J.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Pre- and postexposure efficacy of fully human antibodies against spike protein in a novel humanized mouse model of MERS-CoV infection</article-title>. <source>Proc. Natl. Acad. Sci. USA</source><volume>112</volume>, <fpage>8738</fpage>–<lpage>8743</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.1510830112</pub-id>, PMID: <pub-id pub-id-type="pmid">26124093</pub-id></mixed-citation></ref><ref id="ref114"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paules</surname><given-names>C. I.</given-names></name><name><surname>Lakdawala</surname><given-names>S.</given-names></name><name><surname>McAuliffe</surname><given-names>J. M.</given-names></name><name><surname>Paskel</surname><given-names>M.</given-names></name><name><surname>Vogel</surname><given-names>L.</given-names></name><name><surname>Kallewaard</surname><given-names>N. L.</given-names></name><etal></etal></person-group>. (<year>2017</year>). <article-title>The hemagglutinin A stem antibody MEDI8852 prevents and controls disease and limits transmission of pandemic influenza viruses</article-title>. <source>J. Infect. Dis.</source><volume>216</volume>, <fpage>356</fpage>–<lpage>365</lpage>. <pub-id pub-id-type="doi">10.1093/infdis/jix292</pub-id>, PMID: <pub-id pub-id-type="pmid">28633457</pub-id></mixed-citation></ref><ref id="ref115"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Petersen</surname><given-names>E.</given-names></name><name><surname>Hui</surname><given-names>D. S.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name><name><surname>Zumla</surname><given-names>A.</given-names></name></person-group> (<year>2015</year>). <article-title>Middle East respiratory syndrome – advancing the public health and research agenda on MERS – lessons from the South Korea outbreak</article-title>. <source>Int. J. Infect. Dis.</source><volume>36</volume>, <fpage>54</fpage>–<lpage>55</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijid.2015.06.004</pub-id>, PMID: <pub-id pub-id-type="pmid">26072036</pub-id></mixed-citation></ref><ref id="ref116"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pielak</surname><given-names>R. M.</given-names></name><name><surname>Chou</surname><given-names>J. J.</given-names></name></person-group> (<year>2011</year>). <article-title>Influenza M2 proton channels</article-title>. <source>Biochim. Biophys. Acta</source><volume>1808</volume>, <fpage>522</fpage>–<lpage>529</lpage>. <pub-id pub-id-type="doi">10.1016/j.bbamem.2010.04.015</pub-id><pub-id pub-id-type="pmid">20451491</pub-id></mixed-citation></ref><ref id="ref117"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Putri</surname><given-names>W.</given-names></name><name><surname>Muscatello</surname><given-names>D. J.</given-names></name><name><surname>Stockwell</surname><given-names>M. S.</given-names></name><name><surname>Newall</surname><given-names>A. T.</given-names></name></person-group> (<year>2018</year>). <article-title>Economic burden of seasonal influenza in the United States</article-title>. <source>Vaccine</source><volume>36</volume>, <fpage>3960</fpage>–<lpage>3966</lpage>. <pub-id pub-id-type="doi">10.1016/j.vaccine.2018.05.057</pub-id>, PMID: <pub-id pub-id-type="pmid">29801998</pub-id></mixed-citation></ref><ref id="ref118"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rabaan</surname><given-names>A. A.</given-names></name></person-group> (<year>2017</year>). <article-title>Middle East respiratory syndrome coronavirus: five years later</article-title>. <source>Expert Rev. Respir. Med.</source><volume>11</volume>, <fpage>901</fpage>–<lpage>912</lpage>. <pub-id pub-id-type="doi">10.1080/17476348.2017.1367288</pub-id>, PMID: <pub-id pub-id-type="pmid">28826284</pub-id></mixed-citation></ref><ref id="ref119"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rabaan</surname><given-names>A. A.</given-names></name><name><surname>Alahmed</surname><given-names>S. H.</given-names></name><name><surname>Bazzi</surname><given-names>A. M.</given-names></name><name><surname>Alhani</surname><given-names>H. M.</given-names></name></person-group> (<year>2017</year>). <article-title>A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective</article-title>. <source>J. Med. Microbiol.</source><volume>66</volume>, <fpage>1261</fpage>–<lpage>1274</lpage>. <pub-id pub-id-type="doi">10.1099/jmm.0.000565</pub-id>, PMID: <pub-id pub-id-type="pmid">28855003</pub-id></mixed-citation></ref><ref id="ref120"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rossignol</surname><given-names>J. F.</given-names></name></person-group> (<year>2009</year>). <article-title>Thiazolides: a new class of antiviral drugs</article-title>. <source>Expert Opin. Drug Metab. Toxicol.</source><volume>5</volume>, <fpage>667</fpage>–<lpage>674</lpage>. <pub-id pub-id-type="doi">10.1517/17425250902988487</pub-id>, PMID: <pub-id pub-id-type="pmid">19442032</pub-id></mixed-citation></ref><ref id="ref121"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rossignol</surname><given-names>J. F.</given-names></name><name><surname>La Frazia</surname><given-names>S.</given-names></name><name><surname>Chiappa</surname><given-names>L.</given-names></name><name><surname>Ciucci</surname><given-names>A.</given-names></name><name><surname>Santoro</surname><given-names>M. G.</given-names></name></person-group> (<year>2009</year>). <article-title>Thiazolides, a new class of anti-influenza molecules targeting viral hemagglutinin at the post-translational level</article-title>. <source>J. Biol. Chem.</source><volume>284</volume>, <fpage>29798</fpage>–<lpage>29808</lpage>. <pub-id pub-id-type="doi">10.1074/jbc.M109.029470</pub-id>, PMID: <pub-id pub-id-type="pmid">19638339</pub-id></mixed-citation></ref><ref id="ref122"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rouan</surname><given-names>M.-C.</given-names></name><name><surname>Gevers</surname><given-names>T.</given-names></name><name><surname>Roymans</surname><given-names>D.</given-names></name><name><surname>De Zwart</surname><given-names>L.</given-names></name><name><surname>Nauwelaers</surname><given-names>D.</given-names></name><name><surname>De Meulder</surname><given-names>M.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Pharmacokinetics-pharmacodynamics of a respiratory syncytial virus fusion inhibitor in the cotton rat model</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>54</volume>, <fpage>4534</fpage>–<lpage>4539</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.00643-10</pub-id><pub-id pub-id-type="pmid">20823290</pub-id></mixed-citation></ref><ref id="ref123"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Roymans</surname><given-names>D.</given-names></name><name><surname>Rigaux</surname><given-names>P.</given-names></name><name><surname>Kwanten</surname><given-names>L.</given-names></name><name><surname>Vandesteene</surname><given-names>C.</given-names></name><name><surname>Van Ginderen</surname><given-names>M.</given-names></name><name><surname>Van Den Berg</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2014</year>). “<article-title>Discovery of JNJ-53718678, a potent inhibitor of RSV</article-title>” in <source>9th international respiratory syncytial virus symposium</source> (<publisher-loc>Cape Town</publisher-loc>), <fpage>9</fpage>–<lpage>13</lpage>.</mixed-citation></ref><ref id="ref124"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Samuel</surname><given-names>D.</given-names></name><name><surname>Xing</surname><given-names>W.</given-names></name><name><surname>Niedziela-Majka</surname><given-names>A.</given-names></name><name><surname>Wong</surname><given-names>J. S.</given-names></name><name><surname>Hung</surname><given-names>M.</given-names></name><name><surname>Brendza</surname><given-names>K. M.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>GS-5806 inhibits pre-to postfusion conformational changes of the respiratory syncytial virus fusion protein</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>59</volume>, <fpage>7109</fpage>–<lpage>7112</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.00761-15</pub-id>, PMID: <pub-id pub-id-type="pmid">26324264</pub-id></mixed-citation></ref><ref id="ref125"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schickli</surname><given-names>J. H.</given-names></name><name><surname>Whitacre</surname><given-names>D. C.</given-names></name><name><surname>Tang</surname><given-names>R. S.</given-names></name><name><surname>Kaur</surname><given-names>J.</given-names></name><name><surname>Lawlor</surname><given-names>H.</given-names></name><name><surname>Peters</surname><given-names>C. J.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Palivizumab epitope-displaying virus-like particles protect rodents from RSV challenge</article-title>. <source>J. Clin. Invest.</source><volume>125</volume>, <fpage>1637</fpage>–<lpage>1647</lpage>. <pub-id pub-id-type="doi">10.1172/JCI78450</pub-id>, PMID: <pub-id pub-id-type="pmid">25751145</pub-id></mixed-citation></ref><ref id="ref126"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schnell</surname><given-names>J. R.</given-names></name><name><surname>Chou</surname><given-names>J. J.</given-names></name></person-group> (<year>2008</year>). <article-title>Structure and mechanism of the M2 proton channel of influenza A virus</article-title>. <source>Nature</source><volume>451</volume>, <fpage>591</fpage>–<lpage>595</lpage>. <pub-id pub-id-type="doi">10.1038/nature06531</pub-id>, PMID: <pub-id pub-id-type="pmid">18235503</pub-id></mixed-citation></ref><ref id="ref127"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shahabi</surname><given-names>A.</given-names></name><name><surname>Peneva</surname><given-names>D.</given-names></name><name><surname>Incerti</surname><given-names>D.</given-names></name><name><surname>McLaurin</surname><given-names>K.</given-names></name><name><surname>Stevens</surname><given-names>W.</given-names></name></person-group> (<year>2017</year>). <article-title>Assessing variation in the cost of palivizumab for respiratory syncytial virus prevention in preterm infants</article-title>. <source>PharmacoEconomics-Open</source><volume>2</volume>, <fpage>1</fpage>–<lpage>9</lpage>. <pub-id pub-id-type="doi">10.1007/s41669-017-0042-3</pub-id></mixed-citation></ref><ref id="ref128"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shalhoub</surname><given-names>S.</given-names></name><name><surname>Farahat</surname><given-names>F.</given-names></name><name><surname>Al-Jiffri</surname><given-names>A.</given-names></name><name><surname>Simhairi</surname><given-names>R.</given-names></name><name><surname>Shamma</surname><given-names>O.</given-names></name><name><surname>Siddiqi</surname><given-names>N.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>IFN-alpha2a or IFN-beta1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study</article-title>. <source>J. Antimicrob. Chemother.</source><volume>70</volume>, <fpage>2129</fpage>–<lpage>2132</lpage>. <pub-id pub-id-type="doi">10.1093/jac/dkv085</pub-id>, PMID: <pub-id pub-id-type="pmid">25900158</pub-id></mixed-citation></ref><ref id="ref129"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shaw</surname><given-names>M. L.</given-names></name></person-group> (<year>2017</year>). <article-title>The next wave of influenza drugs</article-title>. <source>ACS Infect. Dis.</source><volume>3</volume>, <fpage>691</fpage>–<lpage>694</lpage>. <pub-id pub-id-type="doi">10.1021/acsinfecdis.7b00142</pub-id>, PMID: <pub-id pub-id-type="pmid">28892353</pub-id></mixed-citation></ref><ref id="ref130"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sidwell</surname><given-names>R. W.</given-names></name><name><surname>Barnard</surname><given-names>D. L.</given-names></name><name><surname>Day</surname><given-names>C. W.</given-names></name><name><surname>Smee</surname><given-names>D. F.</given-names></name><name><surname>Bailey</surname><given-names>K. W.</given-names></name><name><surname>Wong</surname><given-names>M. H.</given-names></name><etal></etal></person-group>. (<year>2007</year>). <article-title>Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>51</volume>, <fpage>845</fpage>–<lpage>851</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.01051-06</pub-id>, PMID: <pub-id pub-id-type="pmid">17194832</pub-id></mixed-citation></ref><ref id="ref131"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Sivapalasingam</surname><given-names>S.</given-names></name><name><surname>Caballero-Perez</surname><given-names>D.</given-names></name><name><surname>Houghton</surname><given-names>M.</given-names></name><name><surname>Yang</surname><given-names>F.</given-names></name><name><surname>Davis</surname><given-names>J.</given-names></name><name><surname>Gao</surname><given-names>B.</given-names></name><etal></etal></person-group> (<year>2015</year>). “<article-title>Phase 1 study evaluating safety, tolerability, pharmacokinetics and immunogenicity of REGN2222 in healthy adults: a new human monoclonal RSV-F antibody for RSV prevention</article-title>” in <source>Open forum infectious diseases</source> (<publisher-loc>San Diego, CA</publisher-loc>: <publisher-name>Oxford University Press</publisher-name>).</mixed-citation></ref><ref id="ref132"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sleeman</surname><given-names>K.</given-names></name><name><surname>Mishin</surname><given-names>V. P.</given-names></name><name><surname>Guo</surname><given-names>Z.</given-names></name><name><surname>Garten</surname><given-names>R. J.</given-names></name><name><surname>Balish</surname><given-names>A.</given-names></name><name><surname>Fry</surname><given-names>A. M.</given-names></name><etal></etal></person-group>. (<year>2014</year>). <article-title>Antiviral susceptibility of variant influenza A(H3N2)v viruses isolated in the United States from 2011 to 2013</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>58</volume>, <fpage>2045</fpage>–<lpage>2051</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.02556-13</pub-id>, PMID: <pub-id pub-id-type="pmid">24449767</pub-id></mixed-citation></ref><ref id="ref133"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smee</surname><given-names>D. F.</given-names></name><name><surname>Barnard</surname><given-names>D. L.</given-names></name><name><surname>Jones</surname><given-names>S. M.</given-names></name></person-group> (<year>2016</year>). <article-title>Activities of JNJ63623872 and oseltamivir against influenza A H1N1pdm and H3N2 virus infections in mice</article-title>. <source>Antiviral Res.</source><volume>136</volume>, <fpage>45</fpage>–<lpage>50</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2016.10.009</pub-id>, PMID: <pub-id pub-id-type="pmid">27771390</pub-id></mixed-citation></ref><ref id="ref134"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smee</surname><given-names>D. F.</given-names></name><name><surname>Hurst</surname><given-names>B. L.</given-names></name><name><surname>Wong</surname><given-names>M. H.</given-names></name><name><surname>Bailey</surname><given-names>K. W.</given-names></name><name><surname>Tarbet</surname><given-names>E. B.</given-names></name><name><surname>Morrey</surname><given-names>J. D.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Effects of the combination of favipiravir (T-705) and oseltamivir on influenza A virus infections in mice</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>54</volume>, <fpage>126</fpage>–<lpage>133</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.00933-09</pub-id><pub-id pub-id-type="pmid">19901093</pub-id></mixed-citation></ref><ref id="ref135"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stachulski</surname><given-names>A. V.</given-names></name><name><surname>Santoro</surname><given-names>M. G.</given-names></name><name><surname>Piacentini</surname><given-names>S.</given-names></name><name><surname>Belardo</surname><given-names>G.</given-names></name><name><surname>Frazia</surname><given-names>S.</given-names></name><name><surname>Pidathala</surname><given-names>C.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus</article-title>. <source>Future Med. Chem.</source><volume>10</volume>, <fpage>851</fpage>–<lpage>862</lpage>. <pub-id pub-id-type="doi">10.4155/fmc-2017-0217</pub-id>, PMID: <pub-id pub-id-type="pmid">29629834</pub-id></mixed-citation></ref><ref id="ref136"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sun</surname><given-names>Z.</given-names></name><name><surname>Pan</surname><given-names>Y.</given-names></name><name><surname>Jiang</surname><given-names>S.</given-names></name><name><surname>Lu</surname><given-names>L.</given-names></name></person-group> (<year>2013</year>). <article-title>Respiratory syncytial virus entry inhibitors targeting the F protein</article-title>. <source>Viruses</source><volume>5</volume>, <fpage>211</fpage>–<lpage>225</lpage>. <pub-id pub-id-type="doi">10.3390/v5010211</pub-id>, PMID: <pub-id pub-id-type="pmid">23325327</pub-id></mixed-citation></ref><ref id="ref137"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Takashita</surname><given-names>E.</given-names></name><name><surname>Ejima</surname><given-names>M.</given-names></name><name><surname>Ogawa</surname><given-names>R.</given-names></name><name><surname>Fujisaki</surname><given-names>S.</given-names></name><name><surname>Neumann</surname><given-names>G.</given-names></name><name><surname>Furuta</surname><given-names>Y.</given-names></name><etal></etal></person-group>. (<year>2016</year>). <article-title>Antiviral susceptibility of influenza viruses isolated from patients pre- and post-administration of favipiravir</article-title>. <source>Antiviral Res.</source><volume>132</volume>, <fpage>170</fpage>–<lpage>177</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2016.06.007</pub-id>, PMID: <pub-id pub-id-type="pmid">27321665</pub-id></mixed-citation></ref><ref id="ref138"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Takashita</surname><given-names>E.</given-names></name><name><surname>Kiso</surname><given-names>M.</given-names></name><name><surname>Fujisaki</surname><given-names>S.</given-names></name><name><surname>Yokoyama</surname><given-names>M.</given-names></name><name><surname>Nakamura</surname><given-names>K.</given-names></name><name><surname>Shirakura</surname><given-names>M.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Characterization of a large cluster of influenza A(H1N1)pdm09 viruses cross-resistant to oseltamivir and peramivir during the 2013-2014 influenza season in Japan</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>59</volume>, <fpage>2607</fpage>–<lpage>2617</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.04836-14</pub-id>, PMID: <pub-id pub-id-type="pmid">25691635</pub-id></mixed-citation></ref><ref id="ref139"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Takashita</surname><given-names>E.</given-names></name><name><surname>Morita</surname><given-names>H.</given-names></name><name><surname>Ogawa</surname><given-names>R.</given-names></name><name><surname>Nakamura</surname><given-names>K.</given-names></name><name><surname>Fujisaki</surname><given-names>S.</given-names></name><name><surname>Shirakura</surname><given-names>M.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>Susceptibility of influenza viruses to the novel cap-dependent endonuclease inhibitor Baloxavir Marboxil</article-title>. <source>Front. Microbiol.</source><volume>9</volume>:<fpage>3026</fpage>. <pub-id pub-id-type="doi">10.3389/fmicb.2018.03026</pub-id><pub-id pub-id-type="pmid">30574137</pub-id></mixed-citation></ref><ref id="ref140"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Taleb</surname><given-names>S. A.</given-names></name><name><surname>Al Thani</surname><given-names>A. A.</given-names></name><name><surname>Al Ansari</surname><given-names>K.</given-names></name><name><surname>Yassine</surname><given-names>H. M.</given-names></name></person-group> (<year>2018</year>). <article-title>Human respiratory syncytial virus: pathogenesis, immune responses, and current vaccine approaches</article-title>. <source>Eur. J. Clin. Microbiol. Infect. Dis.</source><volume>37</volume>, <fpage>1</fpage>–<lpage>11</lpage>. <pub-id pub-id-type="doi">10.1007/s10096-018-3289-4</pub-id><pub-id pub-id-type="pmid">28795339</pub-id></mixed-citation></ref><ref id="ref141"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tarbet</surname><given-names>E. B.</given-names></name><name><surname>Maekawa</surname><given-names>M.</given-names></name><name><surname>Furuta</surname><given-names>Y.</given-names></name><name><surname>Babu</surname><given-names>Y. S.</given-names></name><name><surname>Morrey</surname><given-names>J. D.</given-names></name><name><surname>Smee</surname><given-names>D. F.</given-names></name></person-group> (<year>2012</year>). <article-title>Combinations of favipiravir and peramivir for the treatment of pandemic influenza A/California/04/2009 (H1N1) virus infections in mice</article-title>. <source>Antiviral Res.</source><volume>94</volume>, <fpage>103</fpage>–<lpage>110</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2012.03.001</pub-id>, PMID: <pub-id pub-id-type="pmid">22429564</pub-id></mixed-citation></ref><ref id="ref142"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tharakaraman</surname><given-names>K.</given-names></name><name><surname>Subramanian</surname><given-names>V.</given-names></name><name><surname>Cain</surname><given-names>D.</given-names></name><name><surname>Sasisekharan</surname><given-names>V.</given-names></name><name><surname>Sasisekharan</surname><given-names>R.</given-names></name></person-group> (<year>2014</year>). <article-title>Broadly neutralizing influenza hemagglutinin stem-specific antibody CR8020 targets residues that are prone to escape due to host selection pressure</article-title>. <source>Cell Host Microbe</source><volume>15</volume>, <fpage>644</fpage>–<lpage>651</lpage>. <pub-id pub-id-type="doi">10.1016/j.chom.2014.04.009</pub-id>, PMID: <pub-id pub-id-type="pmid">24832457</pub-id></mixed-citation></ref><ref id="ref143"><mixed-citation publication-type="journal"><person-group person-group-type="author"><collab id="coll7">The PREVENT Study Group</collab></person-group> (<year>1997</year>). <article-title>Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis</article-title>. <source>Pediatrics</source><volume>99</volume>, <fpage>93</fpage>–<lpage>99</lpage>. <pub-id pub-id-type="doi">10.1542/peds.99.1.93</pub-id>, PMID: <pub-id pub-id-type="pmid">8989345</pub-id></mixed-citation></ref><ref id="ref144"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tian</surname><given-names>D.</given-names></name><name><surname>Battles</surname><given-names>M. B.</given-names></name><name><surname>Moin</surname><given-names>S. M.</given-names></name><name><surname>Chen</surname><given-names>M.</given-names></name><name><surname>Modjarrad</surname><given-names>K.</given-names></name><name><surname>Kumar</surname><given-names>A.</given-names></name><etal></etal></person-group>. (<year>2017</year>). <article-title>Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein</article-title>. <source>Nat. Commun.</source><volume>8</volume>:<fpage>1877</fpage>. <pub-id pub-id-type="doi">10.1038/s41467-017-01858-w</pub-id>, PMID: <pub-id pub-id-type="pmid">29187732</pub-id></mixed-citation></ref><ref id="ref145"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tilmanis</surname><given-names>D.</given-names></name><name><surname>Van Baalen</surname><given-names>C.</given-names></name><name><surname>Oh</surname><given-names>D. Y.</given-names></name><name><surname>Rossignol</surname><given-names>J. F.</given-names></name><name><surname>Hurt</surname><given-names>A. C.</given-names></name></person-group> (<year>2017</year>). <article-title>The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide</article-title>. <source>Antiviral Res.</source><volume>147</volume>, <fpage>142</fpage>–<lpage>148</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2017.10.002</pub-id>, PMID: <pub-id pub-id-type="pmid">28986103</pub-id></mixed-citation></ref><ref id="ref146"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Toovey</surname><given-names>S.</given-names></name><name><surname>Wu</surname><given-names>J.</given-names></name><name><surname>Wang</surname><given-names>V.</given-names></name><name><surname>Griffin</surname><given-names>P.</given-names></name><name><surname>Lau</surname><given-names>A.</given-names></name><name><surname>Elliot</surname><given-names>S.</given-names></name></person-group> (<year>2015</year>). “<article-title>Safety and pharmacokinetics in healthy volunteers of the anti-RSV antiviral AK0529</article-title>” in <source>1st international meeting on respiratory pathogens, September 3th, Singapore.</source><publisher-name>International Society for Influenza and other Respiratory Virus Diseases (ISIRV).</publisher-name></mixed-citation></ref><ref id="ref147"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Trevejo</surname><given-names>J. M.</given-names></name><name><surname>Asmal</surname><given-names>M.</given-names></name><name><surname>Vingerhoets</surname><given-names>J.</given-names></name><name><surname>Polo</surname><given-names>R.</given-names></name><name><surname>Robertson</surname><given-names>S.</given-names></name><name><surname>Jiang</surname><given-names>Y.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Pimodivir treatment in adult volunteers experimentally inoculated with live influenza virus: a phase IIa, randomized, double-blind, placebo-controlled study</article-title>. <source>Antivir. Ther.</source><volume>23</volume>, <fpage>335</fpage>–<lpage>344</lpage>. <pub-id pub-id-type="doi">10.3851/IMP3212</pub-id>, PMID: <pub-id pub-id-type="pmid">29244026</pub-id></mixed-citation></ref><ref id="ref148"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Triana-Baltzer</surname><given-names>G. B.</given-names></name><name><surname>Babizki</surname><given-names>M.</given-names></name><name><surname>Chan</surname><given-names>M. C.</given-names></name><name><surname>Wong</surname><given-names>A. C.</given-names></name><name><surname>Aschenbrenner</surname><given-names>L. M.</given-names></name><name><surname>Campbell</surname><given-names>E. R.</given-names></name><etal></etal></person-group>. (<year>2010</year>). <article-title>DAS181, a sialidase fusion protein, protects human airway epithelium against influenza virus infection: an in vitro pharmacodynamic analysis</article-title>. <source>J. Antimicrob. Chemother.</source><volume>65</volume>, <fpage>275</fpage>–<lpage>284</lpage>. <pub-id pub-id-type="doi">10.1093/jac/dkp421</pub-id>, PMID: <pub-id pub-id-type="pmid">19942616</pub-id></mixed-citation></ref><ref id="ref149"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Triana-Baltzer</surname><given-names>G. B.</given-names></name><name><surname>Gubareva</surname><given-names>L. V.</given-names></name><name><surname>Nicholls</surname><given-names>J. M.</given-names></name><name><surname>Pearce</surname><given-names>M. B.</given-names></name><name><surname>Mishin</surname><given-names>V. P.</given-names></name><name><surname>Belser</surname><given-names>J. A.</given-names></name><etal></etal></person-group>. (<year>2009</year>). <article-title>Novel pandemic influenza A(H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein</article-title>. <source>PLoS One</source><volume>4</volume>:<fpage>e7788</fpage>. <pub-id pub-id-type="doi">10.1371/journal.pone.0007838</pub-id>, PMID: <pub-id pub-id-type="pmid">19893747</pub-id></mixed-citation></ref><ref id="ref150"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Triana-Baltzer</surname><given-names>G. B.</given-names></name><name><surname>Sanders</surname><given-names>R. L.</given-names></name><name><surname>Hedlund</surname><given-names>M.</given-names></name><name><surname>Jensen</surname><given-names>K. A.</given-names></name><name><surname>Aschenbrenner</surname><given-names>L. M.</given-names></name><name><surname>Larson</surname><given-names>J. L.</given-names></name><etal></etal></person-group>. (<year>2011</year>). <article-title>Phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein DAS181</article-title>. <source>J. Antimicrob. Chemother.</source><volume>66</volume>, <fpage>15</fpage>–<lpage>28</lpage>. <pub-id pub-id-type="doi">10.1093/jac/dkq387</pub-id>, PMID: <pub-id pub-id-type="pmid">21097900</pub-id></mixed-citation></ref><ref id="ref151"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Uehara</surname><given-names>T.</given-names></name><name><surname>Keiko</surname><given-names>K.</given-names></name><name><surname>Kawaguchi</surname><given-names>K.</given-names></name><name><surname>Sato</surname><given-names>C.</given-names></name><name><surname>Ishida</surname><given-names>T.</given-names></name><name><surname>Hirotsu</surname><given-names>N.</given-names></name><etal></etal></person-group> (<year>2016</year>). “<article-title>S-033188, a small molecule inhibitor of cap-dependent endonuclease of influenza A and B virus, leads to rapid and profund viral load reduction</article-title>” in <source>Options for the control of influenza IX</source> (<publisher-loc>Chicago, USA</publisher-loc>: <publisher-name>ISIRV</publisher-name>), <fpage>77</fpage>.</mixed-citation></ref><ref id="ref152"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Van Heeke</surname><given-names>G.</given-names></name><name><surname>Allosery</surname><given-names>K.</given-names></name><name><surname>De Brabandere</surname><given-names>V.</given-names></name><name><surname>De Smedt</surname><given-names>T.</given-names></name><name><surname>Detalle</surname><given-names>L.</given-names></name><name><surname>De Fougerolles</surname><given-names>A.</given-names></name></person-group> (<year>2017</year>). <article-title>Nanobodies® as inhaled biotherapeutics for lung diseases</article-title>. <source>Pharmacol. Ther.</source><volume>169</volume>, <fpage>47</fpage>–<lpage>56</lpage>. <pub-id pub-id-type="doi">10.1016/j.pharmthera.2016.06.012</pub-id>, PMID: <pub-id pub-id-type="pmid">27373507</pub-id></mixed-citation></ref><ref id="ref153"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>J.</given-names></name><name><surname>Pielak</surname><given-names>R. M.</given-names></name><name><surname>McClintock</surname><given-names>M. A.</given-names></name><name><surname>Chou</surname><given-names>J. J.</given-names></name></person-group> (<year>2009</year>). <article-title>Solution structure and functional analysis of the influenza B proton channel</article-title>. <source>Nat. Struct. Mol. Biol.</source><volume>16</volume>, <fpage>1267</fpage>–<lpage>1271</lpage>. <pub-id pub-id-type="doi">10.1038/nsmb.1707</pub-id>, PMID: <pub-id pub-id-type="pmid">19898475</pub-id></mixed-citation></ref><ref id="ref154"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wasserman</surname><given-names>R. L.</given-names></name><name><surname>Greener</surname><given-names>B. N.</given-names></name><name><surname>Mond</surname><given-names>J.</given-names></name></person-group> (<year>2017</year>). <article-title>RI-002, an intravenous immunoglobulin containing high titer neutralizing antibody to RSV and other respiratory viruses for use in primary immunodeficiency disease and other immune compromised populations</article-title>. <source>Expert Rev. Clin. Immunol.</source><volume>13</volume>, <fpage>1107</fpage>–<lpage>1119</lpage>. <pub-id pub-id-type="doi">10.1080/1744666X.2017.1389647</pub-id>, PMID: <pub-id pub-id-type="pmid">29035131</pub-id></mixed-citation></ref><ref id="ref155"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Watanabe</surname><given-names>T.</given-names></name><name><surname>Kiso</surname><given-names>M.</given-names></name><name><surname>Fukuyama</surname><given-names>S.</given-names></name><name><surname>Nakajima</surname><given-names>N.</given-names></name><name><surname>Imai</surname><given-names>M.</given-names></name><name><surname>Yamada</surname><given-names>S.</given-names></name><etal></etal></person-group>. (<year>2013</year>). <article-title>Characterization of H7N9 influenza A viruses isolated from humans</article-title>. <source>Nature</source><volume>501</volume>, <fpage>551</fpage>–<lpage>555</lpage>. <pub-id pub-id-type="doi">10.1038/nature12392</pub-id>, PMID: <pub-id pub-id-type="pmid">23842494</pub-id></mixed-citation></ref><ref id="ref156"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wernery</surname><given-names>U.</given-names></name><name><surname>Lau</surname><given-names>S. K.</given-names></name><name><surname>Woo</surname><given-names>P. C.</given-names></name></person-group> (<year>2017</year>). <article-title>Middle East respiratory syndrome (MERS) coronavirus and dromedaries</article-title>. <source>Vet. J.</source><volume>220</volume>, <fpage>75</fpage>–<lpage>79</lpage>. <pub-id pub-id-type="doi">10.1016/j.tvjl.2016.12.020</pub-id>, PMID: <pub-id pub-id-type="pmid">28190501</pub-id></mixed-citation></ref><ref id="ref157"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Widagdo</surname><given-names>W.</given-names></name><name><surname>Okba</surname><given-names>N. M. A.</given-names></name><name><surname>Stalin Raj</surname><given-names>V.</given-names></name><name><surname>Haagmans</surname><given-names>B. L.</given-names></name></person-group> (<year>2017</year>). <article-title>MERS-coronavirus: from discovery to intervention</article-title>. <source>One Health</source><volume>3</volume>, <fpage>11</fpage>–<lpage>16</lpage>. <pub-id pub-id-type="doi">10.1016/j.onehlt.2016.12.001</pub-id>, PMID: <pub-id pub-id-type="pmid">28616497</pub-id></mixed-citation></ref><ref id="ref158"><mixed-citation publication-type="other"><person-group person-group-type="author"><collab id="coll8">World Health Organization</collab></person-group> (<year>2014</year>). <article-title>Position paper on collection and use of convalescent plasma or serum as an element in Middle East Respiratory Syndrome Coronavirus response</article-title>. <comment>Available at:</comment><ext-link ext-link-type="uri" xlink:href="https://www.who.int/bloodproducts/brn/BRN_PositionPaperConvPlasmaMERSCoV_March2014.pdf?ua=1">https://www.who.int/bloodproducts/brn/BRN_PositionPaperConvPlasmaMERSCoV_March2014.pdf?ua=1</ext-link><comment>(Accessed March 11, 2014)</comment>.</mixed-citation></ref><ref id="ref159"><mixed-citation publication-type="other"><person-group person-group-type="author"><collab id="coll9">World Health Organization</collab></person-group> (<year>2017</year>). <article-title>Influenza In Focus: Up to 650000 people die of respiratory diseases linked to seasonal flu each year</article-title>. <comment>Available at:</comment><ext-link ext-link-type="uri" xlink:href="https://www.who.int/en/news-room/detail/14-12-2017-up-to-650-000-people-die-of-respiratory-diseases-linked-to-seasonal-flu-each-year">https://www.who.int/en/news-room/detail/14-12-2017-up-to-650-000-people-die-of-respiratory-diseases-linked-to-seasonal-flu-each-year</ext-link><comment>(Accessed April 17, 2019)</comment>.</mixed-citation></ref><ref id="ref161"><mixed-citation publication-type="other"><person-group person-group-type="author"><collab id="coll11">World Health Organization</collab></person-group> (<year>2019</year>). <article-title>Clinical mamagment of severe acute respiratory infection when MESR-CoV infection is suspected: interim guidance</article-title>. <comment>Available at:</comment><ext-link ext-link-type="uri" xlink:href="http://www.who.int/iris/handle/10665/178529">http://www.who.int/iris/handle/10665/178529</ext-link><comment>(Accessed April 17, 2019)</comment>.</mixed-citation></ref><ref id="ref162"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>X. X.</given-names></name><name><surname>Gao</surname><given-names>H. N.</given-names></name><name><surname>Wu</surname><given-names>H. B.</given-names></name><name><surname>Peng</surname><given-names>X. M.</given-names></name><name><surname>Ou</surname><given-names>H. L.</given-names></name><name><surname>Li</surname><given-names>L. J.</given-names></name></person-group> (<year>2015</year>). <article-title>Successful treatment of avian-origin influenza A (H7N9) infection using convalescent plasma</article-title>. <source>Int. J. Infect. Dis.</source><volume>41</volume>, <fpage>3</fpage>–<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijid.2015.10.009</pub-id>, PMID: <pub-id pub-id-type="pmid">26482389</pub-id></mixed-citation></ref><ref id="ref163"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wu</surname><given-names>H.</given-names></name><name><surname>Pfarr</surname><given-names>D. S.</given-names></name><name><surname>Johnson</surname><given-names>S.</given-names></name><name><surname>Brewah</surname><given-names>Y. A.</given-names></name><name><surname>Woods</surname><given-names>R. M.</given-names></name><name><surname>Patel</surname><given-names>N. K.</given-names></name><etal></etal></person-group>. (<year>2007</year>). <article-title>Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract</article-title>. <source>J. Mol. Biol.</source><volume>368</volume>, <fpage>652</fpage>–<lpage>665</lpage>. <pub-id pub-id-type="doi">10.1016/j.jmb.2007.02.024</pub-id>, PMID: <pub-id pub-id-type="pmid">17362988</pub-id></mixed-citation></ref><ref id="ref164"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wyde</surname><given-names>P. R.</given-names></name><name><surname>Chetty</surname><given-names>S. N.</given-names></name><name><surname>Timmerman</surname><given-names>P.</given-names></name><name><surname>Gilbert</surname><given-names>B. E.</given-names></name><name><surname>Andries</surname><given-names>K.</given-names></name></person-group> (<year>2003</year>). <article-title>Short duration aerosols of JNJ 2408068 (R170591) administered prophylactically or therapeutically protect cotton rats from experimental respiratory syncytial virus infection</article-title>. <source>Antiviral Res.</source><volume>60</volume>, <fpage>221</fpage>–<lpage>231</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2003.07.002</pub-id>, PMID: <pub-id pub-id-type="pmid">14638398</pub-id></mixed-citation></ref><ref id="ref165"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wyde</surname><given-names>P. R.</given-names></name><name><surname>Laquerre</surname><given-names>S.</given-names></name><name><surname>Chetty</surname><given-names>S. N.</given-names></name><name><surname>Gilbert</surname><given-names>B. E.</given-names></name><name><surname>Nitz</surname><given-names>T. J.</given-names></name><name><surname>Pevear</surname><given-names>D. C.</given-names></name></person-group> (<year>2005</year>). <article-title>Antiviral efficacy of VP14637 against respiratory syncytial virus in vitro and in cotton rats following delivery by small droplet aerosol</article-title>. <source>Antiviral Res.</source><volume>178</volume>, <fpage>131</fpage>–<lpage>138</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2005.06.009</pub-id>, PMID: <pub-id pub-id-type="pmid">16112208</pub-id></mixed-citation></ref><ref id="ref166"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xing</surname><given-names>Y.</given-names></name><name><surname>Proesmans</surname><given-names>M.</given-names></name></person-group> (<year>2019</year>). <article-title>New therapies for acute RSV infections: where are we?</article-title><source>Eur. J. Pediatr.</source><volume>68</volume>, <fpage>18</fpage>–<lpage>26</lpage>. <pub-id pub-id-type="doi">10.1007/s00431-018-03310-7</pub-id></mixed-citation></ref><ref id="ref167"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yip</surname><given-names>T. F.</given-names></name><name><surname>Selim</surname><given-names>A. S. M.</given-names></name><name><surname>Lian</surname><given-names>I.</given-names></name><name><surname>Lee</surname><given-names>S. M.</given-names></name></person-group> (<year>2018</year>). <article-title>Advancements in host-based interventions for influenza treatment</article-title>. <source>Front. Immunol.</source><volume>9</volume>:<fpage>1547</fpage>. <pub-id pub-id-type="doi">10.3389/fimmu.2018.01547</pub-id><pub-id pub-id-type="pmid">30042762</pub-id></mixed-citation></ref><ref id="ref168"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zenilman</surname><given-names>J. M.</given-names></name><name><surname>Fuchs</surname><given-names>E. J.</given-names></name><name><surname>Hendrix</surname><given-names>C. W.</given-names></name><name><surname>Radebaugh</surname><given-names>C.</given-names></name><name><surname>Jurao</surname><given-names>R.</given-names></name><name><surname>Nayak</surname><given-names>S. U.</given-names></name><etal></etal></person-group>. (<year>2015</year>). <article-title>Phase 1 clinical trials of DAS181, an inhaled sialidase, in healthy adults</article-title>. <source>Antiviral Res.</source><volume>123</volume>, <fpage>114</fpage>–<lpage>119</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2015.09.008</pub-id>, PMID: <pub-id pub-id-type="pmid">26391974</pub-id></mixed-citation></ref><ref id="ref169"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhao</surname><given-names>J.</given-names></name><name><surname>Perera</surname><given-names>R. A.</given-names></name><name><surname>Kayali</surname><given-names>G.</given-names></name><name><surname>Meyerholz</surname><given-names>D.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name><name><surname>Peiris</surname><given-names>M.</given-names></name></person-group> (<year>2015</year>). <article-title>Passive immunotherapy with dromedary immune serum in an experimental animal model for Middle East respiratory syndrome coronavirus infection</article-title>. <source>J. Virol.</source><volume>89</volume>, <fpage>6117</fpage>–<lpage>6120</lpage>. <pub-id pub-id-type="doi">10.1128/JVI.00446-15</pub-id>, PMID: <pub-id pub-id-type="pmid">25787284</pub-id></mixed-citation></ref><ref id="ref170"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhu</surname><given-names>Q.</given-names></name><name><surname>McAuliffe</surname><given-names>J. M.</given-names></name><name><surname>Patel</surname><given-names>N. K.</given-names></name><name><surname>Palmer-Hill</surname><given-names>F. J.</given-names></name><name><surname>Yang</surname><given-names>C.-F.</given-names></name><name><surname>Liang</surname><given-names>B.</given-names></name><etal></etal></person-group>. (<year>2011</year>). <article-title>Analysis of respiratory syncytial virus preclinical and clinical variants resistant to neutralization by monoclonal antibodies palivizumab and/or motavizumab</article-title>. <source>J. Infect. Dis.</source><volume>203</volume>, <fpage>674</fpage>–<lpage>682</lpage>. <pub-id pub-id-type="doi">10.1093/infdis/jiq100</pub-id>, PMID: <pub-id pub-id-type="pmid">21208913</pub-id></mixed-citation></ref><ref id="ref171"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhurilo</surname><given-names>N. I.</given-names></name><name><surname>Chudinov</surname><given-names>M. V.</given-names></name><name><surname>Matveev</surname><given-names>A. V.</given-names></name><name><surname>Smirnova</surname><given-names>O. S.</given-names></name><name><surname>Konstantinova</surname><given-names>I. D.</given-names></name><name><surname>Miroshnikov</surname><given-names>A. I.</given-names></name><etal></etal></person-group>. (<year>2018</year>). <article-title>Isosteric ribavirin analogues: synthesis and antiviral activities</article-title>. <source>Bioorg. Med. Chem. Lett.</source><volume>28</volume>, <fpage>11</fpage>–<lpage>14</lpage>. <pub-id pub-id-type="doi">10.1016/j.bmcl.2017.11.029</pub-id>, PMID: <pub-id pub-id-type="pmid">29173944</pub-id></mixed-citation></ref><ref id="ref172"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zorc</surname><given-names>J. J.</given-names></name><name><surname>Hall</surname><given-names>C. B.</given-names></name></person-group> (<year>2010</year>). <article-title>Bronchiolitis: recent evidence on diagnosis and management</article-title>. <source>Pediatrics</source><volume>125</volume>, <fpage>2009</fpage>–<lpage>2092</lpage>. <pub-id pub-id-type="doi">10.1542/peds.2009-2092</pub-id></mixed-citation></ref><ref id="ref173"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zumla</surname><given-names>A.</given-names></name><name><surname>Chan</surname><given-names>J. F.</given-names></name><name><surname>Azhar</surname><given-names>E. I.</given-names></name><name><surname>Hui</surname><given-names>D. S.</given-names></name><name><surname>Yuen</surname><given-names>K. Y.</given-names></name></person-group> (<year>2016</year>). <article-title>Coronaviruses – drug discovery and therapeutic options</article-title>. <source>Nat. Rev. Drug Discov.</source><volume>15</volume>, <fpage>327</fpage>–<lpage>347</lpage>. <pub-id pub-id-type="doi">10.1038/nrd.2015.37</pub-id>, PMID: <pub-id pub-id-type="pmid">26868298</pub-id></mixed-citation></ref><ref id="ref174"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zumla</surname><given-names>A.</given-names></name><name><surname>Hui</surname><given-names>D. S.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name></person-group> (<year>2015</year>). <article-title>Middle East respiratory syndrome</article-title>. <source>Lancet</source><volume>386</volume>, <fpage>995</fpage>–<lpage>1007</lpage>. <pub-id pub-id-type="doi">10.1016/S0140-6736(15)60454-8</pub-id>, PMID: <pub-id pub-id-type="pmid">26049252</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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