Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins
Identifieur interne : 001317 ( Pmc/Corpus ); précédent : 001316; suivant : 001318Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins
Auteurs : Yan-Hua Li ; Chen-Yu Hu ; Nan-Ping Wu ; Hang-Ping Yao ; Lan-Juan LiSource :
- Engineering (Beijing, China) [ 2095-8099 ] ; 2019.
Abstract
Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a
Url:
DOI: 10.1016/j.eng.2018.11.035
PubMed: 32288963
PubMed Central: 7104727
Links to Exploration step
PMC:7104727Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins</title><author><name sortKey="Li, Yan Hua" sort="Li, Yan Hua" uniqKey="Li Y" first="Yan-Hua" last="Li">Yan-Hua Li</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author><author><name sortKey="Hu, Chen Yu" sort="Hu, Chen Yu" uniqKey="Hu C" first="Chen-Yu" last="Hu">Chen-Yu Hu</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author><author><name sortKey="Wu, Nan Ping" sort="Wu, Nan Ping" uniqKey="Wu N" first="Nan-Ping" last="Wu">Nan-Ping Wu</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author><author><name sortKey="Yao, Hang Ping" sort="Yao, Hang Ping" uniqKey="Yao H" first="Hang-Ping" last="Yao">Hang-Ping Yao</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author><author><name sortKey="Li, Lan Juan" sort="Li, Lan Juan" uniqKey="Li L" first="Lan-Juan" last="Li">Lan-Juan Li</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32288963</idno><idno type="pmc">7104727</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104727</idno><idno type="RBID">PMC:7104727</idno><idno type="doi">10.1016/j.eng.2018.11.035</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">001317</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001317</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins</title><author><name sortKey="Li, Yan Hua" sort="Li, Yan Hua" uniqKey="Li Y" first="Yan-Hua" last="Li">Yan-Hua Li</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author><author><name sortKey="Hu, Chen Yu" sort="Hu, Chen Yu" uniqKey="Hu C" first="Chen-Yu" last="Hu">Chen-Yu Hu</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author><author><name sortKey="Wu, Nan Ping" sort="Wu, Nan Ping" uniqKey="Wu N" first="Nan-Ping" last="Wu">Nan-Ping Wu</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author><author><name sortKey="Yao, Hang Ping" sort="Yao, Hang Ping" uniqKey="Yao H" first="Hang-Ping" last="Yao">Hang-Ping Yao</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author><author><name sortKey="Li, Lan Juan" sort="Li, Lan Juan" uniqKey="Li L" first="Lan-Juan" last="Li">Lan-Juan Li</name><affiliation><nlm:aff id="af005">State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</nlm:aff></affiliation><affiliation><nlm:aff id="af010">Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</nlm:aff></affiliation></author></analytic><series><title level="j">Engineering (Beijing, China)</title><idno type="ISSN">2095-8099</idno><idno type="eISSN">2096-0026</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>Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a <italic>de novo</italic> coronavirus—MERS-CoV—that is associated with high mortality. However, the mechanism by which MERS-CoV infects humans remains unclear. To date, there is no effective vaccine or antibody for human immunity and treatment, other than the safety and tolerability of the fully human polyclonal Immunoglobulin G (IgG) antibody (SAB-301) as a putative therapeutic agent specific for MERS. Although rapid diagnostic and public health measures are currently being implemented, new cases of MERS-CoV infection are still being reported. Therefore, various effective measures should be taken to prevent the serious impact of similar epidemics in the future. Further investigation of the epidemiology and pathogenesis of the virus, as well as the development of effective therapeutic and prophylactic anti-MERS-CoV infections, is necessary. For this purpose, detailed information on MERS-CoV proteins is needed. In this review, we describe the major structural and nonstructural proteins of MERS-CoV and summarize different potential strategies for limiting the outbreak of MERS-CoV. The combination of computational biology and virology can accelerate the advanced design and development of effective peptide therapeutics against MERS-CoV. In summary, this review provides important information about the progress of the elimination of MERS, from prevention to treatment.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Hui, D S" uniqKey="Hui D">D.S. Hui</name></author><author><name sortKey="Azhar, E I" uniqKey="Azhar E">E.I. Azhar</name></author><author><name sortKey="Kim, Y J" uniqKey="Kim Y">Y.J. Kim</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z.A. Memish</name></author><author><name sortKey="Oh, M D" uniqKey="Oh M">M.D. Oh</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, H" uniqKey="Lee H">H. Lee</name></author><author><name sortKey="Lei, H" uniqKey="Lei H">H. Lei</name></author><author><name sortKey="Santarsiero, B D" uniqKey="Santarsiero B">B.D. Santarsiero</name></author><author><name sortKey="Gatuz, J L" uniqKey="Gatuz J">J.L. Gatuz</name></author><author><name sortKey="Cao, S" uniqKey="Cao S">S. Cao</name></author><author><name sortKey="Rice, A J" uniqKey="Rice A">A.J. Rice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, J" uniqKey="Choi J">J. Choi</name></author><author><name sortKey="Kim, M G" uniqKey="Kim M">M.G. Kim</name></author><author><name sortKey="Oh, Y K" uniqKey="Oh Y">Y.K. Oh</name></author><author><name sortKey="Kim, Y B" uniqKey="Kim Y">Y.B. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. Van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A.D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R.A. Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pallesen, J" uniqKey="Pallesen J">J. Pallesen</name></author><author><name sortKey="Wang, N" uniqKey="Wang N">N. Wang</name></author><author><name sortKey="Corbett, K S" uniqKey="Corbett K">K.S. Corbett</name></author><author><name sortKey="Wrapp, D" uniqKey="Wrapp D">D. Wrapp</name></author><author><name sortKey="Kirchdoerfer, R N" uniqKey="Kirchdoerfer R">R.N. Kirchdoerfer</name></author><author><name sortKey="Turner, H L" uniqKey="Turner H">H.L. Turner</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="Van Boheemen, S" uniqKey="Van Boheemen S">S. Van Boheemen</name></author><author><name sortKey="De Graaf, M" uniqKey="De Graaf M">M. De Graaf</name></author><author><name sortKey="Lauber, C" uniqKey="Lauber C">C. Lauber</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Raj, V S" uniqKey="Raj V">V.S. Raj</name></author><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. Zaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frey, K G" uniqKey="Frey K">K.G. Frey</name></author><author><name sortKey="Redden, C L" uniqKey="Redden C">C.L. Redden</name></author><author><name sortKey="Bishop Lilly, K A" uniqKey="Bishop Lilly K">K.A. Bishop-Lilly</name></author><author><name sortKey="Johnson, R" uniqKey="Johnson R">R. Johnson</name></author><author><name sortKey="Hensley, L E" uniqKey="Hensley L">L.E. Hensley</name></author><author><name sortKey="Raviprakash, K" uniqKey="Raviprakash K">K. Raviprakash</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, J F" uniqKey="Chan J">J.F. Chan</name></author><author><name sortKey="Lau, S K" uniqKey="Lau S">S.K. Lau</name></author><author><name sortKey="To, K K" uniqKey="To K">K.K. To</name></author><author><name sortKey="Cheng, V C" uniqKey="Cheng V">V.C. Cheng</name></author><author><name sortKey="Woo, P C" uniqKey="Woo P">P.C. Woo</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cotten, M" uniqKey="Cotten M">M. Cotten</name></author><author><name sortKey="Lam, T T" uniqKey="Lam T">T.T. Lam</name></author><author><name sortKey="Watson, S J" uniqKey="Watson S">S.J. Watson</name></author><author><name sortKey="Palser, A L" uniqKey="Palser A">A.L. Palser</name></author><author><name sortKey="Petrova, V" uniqKey="Petrova V">V. Petrova</name></author><author><name sortKey="Grant, P" uniqKey="Grant P">P. Grant</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><analytic><author><name sortKey="Li, F" uniqKey="Li F">F. Li</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Farzan, M" uniqKey="Farzan M">M. Farzan</name></author><author><name sortKey="Harrison, S C" uniqKey="Harrison S">S.C. Harrison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L. Du</name></author><author><name sortKey="Kou, Z" uniqKey="Kou Z">Z. Kou</name></author><author><name sortKey="Ma, C" uniqKey="Ma C">C. Ma</name></author><author><name sortKey="Tao, X" uniqKey="Tao X">X. Tao</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G. Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, G" uniqKey="Lu G">G. Lu</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y. Hu</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Qi, J" uniqKey="Qi J">J. Qi</name></author><author><name sortKey="Gao, F" uniqKey="Gao F">F. Gao</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, C" uniqKey="Ma C">C. Ma</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G. Zhao</name></author><author><name sortKey="Tao, X" uniqKey="Tao X">X. Tao</name></author><author><name sortKey="Tseng, C T" uniqKey="Tseng C">C.T. Tseng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mou, H" uniqKey="Mou H">H. Mou</name></author><author><name sortKey="Raj, V S" uniqKey="Raj V">V.S. Raj</name></author><author><name sortKey="Van Kuppeveld, F J" uniqKey="Van Kuppeveld F">F.J. Van Kuppeveld</name></author><author><name sortKey="Rottier, P J" uniqKey="Rottier P">P.J. Rottier</name></author><author><name sortKey="Haagmans, B L" uniqKey="Haagmans B">B.L. Haagmans</name></author><author><name sortKey="Bosch, B J" uniqKey="Bosch B">B.J. Bosch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lan, J" uniqKey="Lan J">J. Lan</name></author><author><name sortKey="Yao, Y" uniqKey="Yao Y">Y. Yao</name></author><author><name sortKey="Deng, Y" uniqKey="Deng Y">Y. Deng</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y. Hu</name></author><author><name sortKey="Bao, L" uniqKey="Bao L">L. Bao</name></author><author><name sortKey="Huang, B" uniqKey="Huang B">B. Huang</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><biblStruct><analytic><author><name sortKey="Lu, L" uniqKey="Lu L">L. Lu</name></author><author><name sortKey="Liu, Q" uniqKey="Liu Q">Q. Liu</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y. Zhu</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K.H. Chan</name></author><author><name sortKey="Qin, L" uniqKey="Qin L">L. Qin</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Millet, J K" uniqKey="Millet J">J.K. Millet</name></author><author><name sortKey="Whittaker, G R" uniqKey="Whittaker G">G.R. Whittaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, G" uniqKey="Lu G">G. Lu</name></author><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q. Wang</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G.F. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Surya, W" uniqKey="Surya W">W. Surya</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Verdia Baguena, C" uniqKey="Verdia Baguena C">C. Verdià-Bàguena</name></author><author><name sortKey="Aguilella, V M" uniqKey="Aguilella V">V.M. Aguilella</name></author><author><name sortKey="Torres, J" uniqKey="Torres J">J. Torres</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Westerbeck, J W" uniqKey="Westerbeck J">J.W. Westerbeck</name></author><author><name sortKey="Machamer, C E" uniqKey="Machamer C">C.E. Machamer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xie, Q" uniqKey="Xie Q">Q. Xie</name></author><author><name sortKey="He, X" uniqKey="He X">X. He</name></author><author><name sortKey="Yang, F" uniqKey="Yang F">F. Yang</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X. Liu</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="Sun, Y" uniqKey="Sun Y">Y. Sun</name></author><author><name sortKey="Qi, J" uniqKey="Qi J">J. Qi</name></author><author><name sortKey="Chu, F" uniqKey="Chu F">F. Chu</name></author><author><name sortKey="Wu, H" uniqKey="Wu H">H. Wu</name></author><author><name sortKey="Gao, F" uniqKey="Gao F">F. Gao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Haan, C A" uniqKey="De Haan C">C.A. De Haan</name></author><author><name sortKey="Rottier, P J" uniqKey="Rottier P">P.J. Rottier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, S C" uniqKey="Lin S">S.C. Lin</name></author><author><name sortKey="Ho, C T" uniqKey="Ho C">C.T. Ho</name></author><author><name sortKey="Chuo, W H" uniqKey="Chuo W">W.H. Chuo</name></author><author><name sortKey="Li, S" uniqKey="Li S">S. Li</name></author><author><name sortKey="Wang, T T" uniqKey="Wang T">T.T. Wang</name></author><author><name sortKey="Lin, C C" uniqKey="Lin C">C.C. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Szelazek, B" uniqKey="Szelazek B">B. Szelazek</name></author><author><name sortKey="Kabala, W" uniqKey="Kabala W">W. Kabala</name></author><author><name sortKey="Kus, K" uniqKey="Kus K">K. Kus</name></author><author><name sortKey="Zdzalik, M" uniqKey="Zdzalik M">M. Zdzalik</name></author><author><name sortKey="Twarda Clapa, A" uniqKey="Twarda Clapa A">A. Twarda-Clapa</name></author><author><name sortKey="Golik, P" uniqKey="Golik P">P. Golik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y. Hu</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Gao, T" uniqKey="Gao T">T. Gao</name></author><author><name sortKey="Cui, Y" uniqKey="Cui Y">Y. Cui</name></author><author><name sortKey="Jin, Y" uniqKey="Jin Y">Y. Jin</name></author><author><name sortKey="Li, P" uniqKey="Li P">P. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grunewald, M E" uniqKey="Grunewald M">M.E. Grunewald</name></author><author><name sortKey="Fehr, A R" uniqKey="Fehr A">A.R. Fehr</name></author><author><name sortKey="Athmer, J" uniqKey="Athmer J">J. Athmer</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Papageorgiou, N" uniqKey="Papageorgiou N">N. Papageorgiou</name></author><author><name sortKey="Lichiere, J" uniqKey="Lichiere J">J. Lichière</name></author><author><name sortKey="Baklouti, A" uniqKey="Baklouti A">A. Baklouti</name></author><author><name sortKey="Ferron, F" uniqKey="Ferron F">F. Ferron</name></author><author><name sortKey="Sevajol, M" uniqKey="Sevajol M">M. Sévajol</name></author><author><name sortKey="Canard, B" uniqKey="Canard B">B. Canard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banda, N K" uniqKey="Banda N">N.K. Banda</name></author><author><name sortKey="Acharya, S" uniqKey="Acharya S">S. Acharya</name></author><author><name sortKey="Scheinman, R I" uniqKey="Scheinman R">R.I. Scheinman</name></author><author><name sortKey="Mehta, G" uniqKey="Mehta G">G. Mehta</name></author><author><name sortKey="Takahashi, M" uniqKey="Takahashi M">M. Takahashi</name></author><author><name sortKey="Endo, Y" uniqKey="Endo Y">Y. Endo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bolwig, G M" uniqKey="Bolwig G">G.M. Bolwig</name></author><author><name sortKey="Bruder, J T" uniqKey="Bruder J">J.T. Bruder</name></author><author><name sortKey="Hearing, P" uniqKey="Hearing P">P. Hearing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Forni, D" uniqKey="Forni D">D. Forni</name></author><author><name sortKey="Cagliani, R" uniqKey="Cagliani R">R. Cagliani</name></author><author><name sortKey="Clerici, M" uniqKey="Clerici M">M. Clerici</name></author><author><name sortKey="Sironi, M" uniqKey="Sironi M">M. Sironi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menachery, V D" uniqKey="Menachery V">V.D. Menachery</name></author><author><name sortKey="Mitchell, H D" uniqKey="Mitchell H">H.D. Mitchell</name></author><author><name sortKey="Cockrell, A S" uniqKey="Cockrell A">A.S. Cockrell</name></author><author><name sortKey="Gralinski, L E" uniqKey="Gralinski L">L.E. Gralinski</name></author><author><name sortKey="Yount, B L" uniqKey="Yount B">B.L. Yount</name></author><author><name sortKey="Graham, R L" uniqKey="Graham R">R.L. Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Geng, H" uniqKey="Geng H">H. Geng</name></author><author><name sortKey="Deng, Y" uniqKey="Deng Y">Y. Deng</name></author><author><name sortKey="Huang, B" uniqKey="Huang B">B. Huang</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y. Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thornbrough, J M" uniqKey="Thornbrough J">J.M. Thornbrough</name></author><author><name sortKey="Jha, B K" uniqKey="Jha B">B.K. Jha</name></author><author><name sortKey="Yount, B" uniqKey="Yount B">B. Yount</name></author><author><name sortKey="Goldstein, S A" uniqKey="Goldstein S">S.A. Goldstein</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Elliott, R" uniqKey="Elliott R">R. Elliott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rabouw, H H" uniqKey="Rabouw H">H.H. Rabouw</name></author><author><name sortKey="Langereis, M A" uniqKey="Langereis M">M.A. Langereis</name></author><author><name sortKey="Knaap, R C" uniqKey="Knaap R">R.C. Knaap</name></author><author><name sortKey="Dalebout, T J" uniqKey="Dalebout T">T.J. Dalebout</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="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="Lei, J" uniqKey="Lei J">J. Lei</name></author><author><name sortKey="Kusov, Y" uniqKey="Kusov Y">Y. Kusov</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baez Santos, Y M" uniqKey="Baez Santos Y">Y.M. Báez-Santos</name></author><author><name sortKey="St John, S E" uniqKey="St John S">S.E. St John</name></author><author><name sortKey="Mesecar, A D" uniqKey="Mesecar A">A.D. Mesecar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kankanamalage, A C G" uniqKey="Kankanamalage A">A.C.G. Kankanamalage</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Damalanka, V C" uniqKey="Damalanka V">V.C. Damalanka</name></author><author><name sortKey="Rathnayake, A D" uniqKey="Rathnayake A">A.D. Rathnayake</name></author><author><name sortKey="Fehr, A R" uniqKey="Fehr A">A.R. Fehr</name></author><author><name sortKey="Mehzabeen, N" uniqKey="Mehzabeen N">N. Mehzabeen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kandeel, M" uniqKey="Kandeel M">M. Kandeel</name></author><author><name sortKey="Altaher, A" uniqKey="Altaher A">A. Altaher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Forni, D" uniqKey="Forni D">D. Forni</name></author><author><name sortKey="Cagliani, R" uniqKey="Cagliani R">R. Cagliani</name></author><author><name sortKey="Mozzi, A" uniqKey="Mozzi A">A. Mozzi</name></author><author><name sortKey="Pozzoli, U" uniqKey="Pozzoli U">U. Pozzoli</name></author><author><name sortKey="Al Daghri, N" uniqKey="Al Daghri N">N. Al-Daghri</name></author><author><name sortKey="Clerici, M" uniqKey="Clerici M">M. Clerici</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oudshoorn, D" uniqKey="Oudshoorn D">D. Oudshoorn</name></author><author><name sortKey="Rijs, K" uniqKey="Rijs K">K. Rijs</name></author><author><name sortKey="Limpens, R W A L" uniqKey="Limpens R">R.W.A.L. Limpens</name></author><author><name sortKey="Groen, K" uniqKey="Groen K">K. Groen</name></author><author><name sortKey="Koster, A J" uniqKey="Koster A">A.J. Koster</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Terada, Y" uniqKey="Terada Y">Y. Terada</name></author><author><name sortKey="Kawachi, K" uniqKey="Kawachi K">K. Kawachi</name></author><author><name sortKey="Matsuura, Y" uniqKey="Matsuura Y">Y. Matsuura</name></author><author><name sortKey="Kamitani, W" uniqKey="Kamitani W">W. Kamitani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, R" uniqKey="Zhang R">R. Zhang</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Cowley, T J" uniqKey="Cowley T">T.J. Cowley</name></author><author><name sortKey="Steinbrenner, A D" uniqKey="Steinbrenner A">A.D. Steinbrenner</name></author><author><name sortKey="Phillips, J M" uniqKey="Phillips J">J.M. Phillips</name></author><author><name sortKey="Yount, B L" uniqKey="Yount B">B.L. Yount</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adedeji, A O" uniqKey="Adedeji A">A.O. Adedeji</name></author><author><name sortKey="Lazarus, H" uniqKey="Lazarus H">H. Lazarus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kindler, E" uniqKey="Kindler E">E. Kindler</name></author><author><name sortKey="Gil Cruz, C" uniqKey="Gil Cruz C">C. Gil-Cruz</name></author><author><name sortKey="Spanier, J" uniqKey="Spanier J">J. Spanier</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Wilhelm, J" uniqKey="Wilhelm J">J. Wilhelm</name></author><author><name sortKey="Rabouw, H H" uniqKey="Rabouw H">H.H. Rabouw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deng, X" uniqKey="Deng X">X. Deng</name></author><author><name sortKey="Hackbart, M" uniqKey="Hackbart M">M. Hackbart</name></author><author><name sortKey="Mettelman, R C" uniqKey="Mettelman R">R.C. Mettelman</name></author><author><name sortKey="O Rien, A" uniqKey="O Rien A">A. O’Brien</name></author><author><name sortKey="Mielech, A M" uniqKey="Mielech A">A.M. Mielech</name></author><author><name sortKey="Yi, G" uniqKey="Yi G">G. Yi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aouadi, W" uniqKey="Aouadi W">W. Aouadi</name></author><author><name sortKey="Blanjoie, A" uniqKey="Blanjoie A">A. Blanjoie</name></author><author><name sortKey="Vasseur, J J" uniqKey="Vasseur J">J.J. Vasseur</name></author><author><name sortKey="Debart, F" uniqKey="Debart F">F. Debart</name></author><author><name sortKey="Canard, B" uniqKey="Canard B">B. Canard</name></author><author><name sortKey="Decroly, E" uniqKey="Decroly E">E. Decroly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Angelini, M M" uniqKey="Angelini M">M.M. Angelini</name></author><author><name sortKey="Akhlaghpour, M" uniqKey="Akhlaghpour M">M. Akhlaghpour</name></author><author><name sortKey="Neuman, B W" uniqKey="Neuman B">B.W. Neuman</name></author><author><name sortKey="Buchmeier, M J" uniqKey="Buchmeier M">M.J. Buchmeier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menachery, V D" uniqKey="Menachery V">V.D. Menachery</name></author><author><name sortKey="Gralinski, L E" uniqKey="Gralinski L">L.E. Gralinski</name></author><author><name sortKey="Mitchell, H D" uniqKey="Mitchell H">H.D. Mitchell</name></author><author><name sortKey="Dinnon, K H" uniqKey="Dinnon K">K.H. Dinnon</name></author><author><name sortKey="Leist, S R" uniqKey="Leist S">S.R. Leist</name></author><author><name sortKey="Yount, B L" uniqKey="Yount B">B.L. Yount</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alfuwaires, M" uniqKey="Alfuwaires M">M. Alfuwaires</name></author><author><name sortKey="Altaher, A" uniqKey="Altaher A">A. Altaher</name></author><author><name sortKey="Kandeel, M" uniqKey="Kandeel M">M. Kandeel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Y P" uniqKey="Huang Y">Y.P. Huang</name></author><author><name sortKey="Cho, C C" uniqKey="Cho C">C.C. Cho</name></author><author><name sortKey="Chang, C F" uniqKey="Chang C">C.F. Chang</name></author><author><name sortKey="Hsu, C H" uniqKey="Hsu C">C.H. Hsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Phua, K K L" uniqKey="Phua K">K.K.L. Phua</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Sim, S H" uniqKey="Sim S">S.H. Sim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qian, W" uniqKey="Qian W">W. Qian</name></author><author><name sortKey="Wei, X" uniqKey="Wei X">X. Wei</name></author><author><name sortKey="Guo, K" uniqKey="Guo K">K. Guo</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Lin, X" uniqKey="Lin X">X. Lin</name></author><author><name sortKey="Zou, Z" uniqKey="Zou Z">Z. Zou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuo, R L" uniqKey="Kuo R">R.L. Kuo</name></author><author><name sortKey="Li, L H" uniqKey="Li L">L.H. Li</name></author><author><name sortKey="Lin, S J" uniqKey="Lin S">S.J. Lin</name></author><author><name sortKey="Li, Z H" uniqKey="Li Z">Z.H. Li</name></author><author><name sortKey="Chen, G W" uniqKey="Chen G">G.W. Chen</name></author><author><name sortKey="Chang, C K" uniqKey="Chang C">C.K. Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schierhorn, K L" uniqKey="Schierhorn K">K.L. Schierhorn</name></author><author><name sortKey="Jolmes, F" uniqKey="Jolmes F">F. Jolmes</name></author><author><name sortKey="Bespalowa, J" uniqKey="Bespalowa J">J. Bespalowa</name></author><author><name sortKey="Saenger, S" uniqKey="Saenger S">S. Saenger</name></author><author><name sortKey="Peteranderl, C" uniqKey="Peteranderl C">C. Peteranderl</name></author><author><name sortKey="Dzieciolowski, J" uniqKey="Dzieciolowski J">J. Dzieciolowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lokugamage, K G" uniqKey="Lokugamage K">K.G. Lokugamage</name></author><author><name sortKey="Narayanan, K" uniqKey="Narayanan K">K. Narayanan</name></author><author><name sortKey="Nakagawa, K" uniqKey="Nakagawa K">K. Nakagawa</name></author><author><name sortKey="Terasaki, K" uniqKey="Terasaki K">K. Terasaki</name></author><author><name sortKey="Ramirez, S I" uniqKey="Ramirez S">S.I. Ramirez</name></author><author><name sortKey="Tseng, C T" uniqKey="Tseng C">C.T. Tseng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peters, H L" uniqKey="Peters H">H.L. Peters</name></author><author><name sortKey="Jochmans, D" uniqKey="Jochmans D">D. Jochmans</name></author><author><name sortKey="De Wilde, A H" uniqKey="De Wilde A">A.H. de Wilde</name></author><author><name sortKey="Posthuma, C C" uniqKey="Posthuma C">C.C. Posthuma</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author><author><name sortKey="Neyts, J" uniqKey="Neyts J">J. Neyts</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dyall, J" uniqKey="Dyall J">J. Dyall</name></author><author><name sortKey="Coleman, C M" uniqKey="Coleman C">C.M. Coleman</name></author><author><name sortKey="Hart, B J" uniqKey="Hart B">B.J. Hart</name></author><author><name sortKey="Venkataraman, T" uniqKey="Venkataraman T">T. Venkataraman</name></author><author><name sortKey="Holbrook, M R" uniqKey="Holbrook M">M.R. Holbrook</name></author><author><name sortKey="Kindrachuk, J" uniqKey="Kindrachuk J">J. Kindrachuk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wilde, A H" uniqKey="De Wilde A">A.H. De Wilde</name></author><author><name sortKey="Raj, V S" uniqKey="Raj V">V.S. Raj</name></author><author><name sortKey="Oudshoorn, D" uniqKey="Oudshoorn D">D. Oudshoorn</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Van Nieuwkoop, S" uniqKey="Van Nieuwkoop S">S. Van Nieuwkoop</name></author><author><name sortKey="Limpens, R W" uniqKey="Limpens R">R.W. Limpens</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="Kim, Y S" uniqKey="Kim Y">Y.S. Kim</name></author><author><name sortKey="Son, A" uniqKey="Son A">A. Son</name></author><author><name sortKey="Kim, J" uniqKey="Kim J">J. Kim</name></author><author><name sortKey="Kwon, S B" uniqKey="Kwon S">S.B. Kwon</name></author><author><name sortKey="Kim, M H" uniqKey="Kim M">M.H. Kim</name></author><author><name sortKey="Kim, P" uniqKey="Kim P">P. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corti, D" uniqKey="Corti D">D. Corti</name></author><author><name sortKey="Passini, N" uniqKey="Passini N">N. Passini</name></author><author><name sortKey="Lanzavecchia, A" uniqKey="Lanzavecchia A">A. Lanzavecchia</name></author><author><name sortKey="Zambon, M" uniqKey="Zambon M">M. Zambon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tang, X C" uniqKey="Tang X">X.C. Tang</name></author><author><name sortKey="Agnihothram, S S" uniqKey="Agnihothram S">S.S. Agnihothram</name></author><author><name sortKey="Jiao, Y" uniqKey="Jiao Y">Y. Jiao</name></author><author><name sortKey="Stanhope, J" uniqKey="Stanhope J">J. Stanhope</name></author><author><name sortKey="Graham, R L" uniqKey="Graham R">R.L. Graham</name></author><author><name sortKey="Peterson, E C" uniqKey="Peterson E">E.C. Peterson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jiang, L" uniqKey="Jiang L">L. Jiang</name></author><author><name sortKey="Wang, N" uniqKey="Wang N">N. Wang</name></author><author><name sortKey="Zuo, T" uniqKey="Zuo T">T. Zuo</name></author><author><name sortKey="Shi, X" uniqKey="Shi X">X. Shi</name></author><author><name sortKey="Poon, K M" uniqKey="Poon K">K.M. Poon</name></author><author><name sortKey="Wu, Y" uniqKey="Wu Y">Y. Wu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Niu, P" uniqKey="Niu P">P. Niu</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S. Zhang</name></author><author><name sortKey="Zhou, P" uniqKey="Zhou P">P. Zhou</name></author><author><name sortKey="Huang, B" uniqKey="Huang B">B. Huang</name></author><author><name sortKey="Deng, Y" uniqKey="Deng Y">Y. Deng</name></author><author><name sortKey="Qin, K" uniqKey="Qin K">K. Qin</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="De Wit, E" uniqKey="De Wit E">E. De Wit</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="Horne, E" uniqKey="Horne E">E. Horne</name></author><author><name sortKey="Haddock, E" uniqKey="Haddock E">E. Haddock</name></author><author><name sortKey="Saturday, G" uniqKey="Saturday G">G. Saturday</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, L" uniqKey="Du L">L. Du</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G. Zhao</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y. Yang</name></author><author><name sortKey="Qiu, H" uniqKey="Qiu H">H. Qiu</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Kou, Z" uniqKey="Kou Z">Z. Kou</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="Qiu, H" uniqKey="Qiu H">H. Qiu</name></author><author><name sortKey="Sun, S" uniqKey="Sun S">S. Sun</name></author><author><name sortKey="Xiao, H" uniqKey="Xiao H">H. Xiao</name></author><author><name sortKey="Feng, J" uniqKey="Feng J">J. Feng</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y. Guo</name></author><author><name sortKey="Tai, W" uniqKey="Tai W">W. Tai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Wan, Y" uniqKey="Wan Y">Y. Wan</name></author><author><name sortKey="Liu, P" uniqKey="Liu P">P. Liu</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Lu, G" uniqKey="Lu G">G. Lu</name></author><author><name sortKey="Qi, J" uniqKey="Qi J">J. Qi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, N" uniqKey="Zhang N">N. Zhang</name></author><author><name sortKey="Channappanavar, R" uniqKey="Channappanavar R">R. Channappanavar</name></author><author><name sortKey="Ma, C" uniqKey="Ma C">C. Ma</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Tang, J" uniqKey="Tang J">J. Tang</name></author><author><name sortKey="Garron, T" uniqKey="Garron T">T. Garron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W. Shi</name></author><author><name sortKey="Joyce, M G" uniqKey="Joyce M">M.G. Joyce</name></author><author><name sortKey="Modjarrad, K" uniqKey="Modjarrad K">K. Modjarrad</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Leung, K" uniqKey="Leung K">K. Leung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K. Shirato</name></author><author><name sortKey="Kawase, M" uniqKey="Kawase M">M. Kawase</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S. Matsuyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gierer, S" uniqKey="Gierer S">S. Gierer</name></author><author><name sortKey="Bertram, S" uniqKey="Bertram S">S. Bertram</name></author><author><name sortKey="Kaup, F" uniqKey="Kaup F">F. Kaup</name></author><author><name sortKey="Wrensch, F" uniqKey="Wrensch F">F. Wrensch</name></author><author><name sortKey="Heurich, A" uniqKey="Heurich A">A. Heurich</name></author><author><name sortKey="Kr Mer Kuhl, A" uniqKey="Kr Mer Kuhl A">A. Krämer-Kühl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Millet, J K" uniqKey="Millet J">J.K. Millet</name></author><author><name sortKey="Whittaker, G R" uniqKey="Whittaker G">G.R. Whittaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coleman, C M" uniqKey="Coleman C">C.M. Coleman</name></author><author><name sortKey="Sisk, J M" uniqKey="Sisk J">J.M. Sisk</name></author><author><name sortKey="Mingo, R M" uniqKey="Mingo R">R.M. Mingo</name></author><author><name sortKey="Nelson, E A" uniqKey="Nelson E">E.A. Nelson</name></author><author><name sortKey="White, J M" uniqKey="White J">J.M. White</name></author><author><name sortKey="Frieman, M B" uniqKey="Frieman M">M.B. Frieman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wrensch, F" uniqKey="Wrensch F">F. Wrensch</name></author><author><name sortKey="Winkler, M" uniqKey="Winkler M">M. Winkler</name></author><author><name sortKey="Pohlmann, S" uniqKey="Pohlmann S">S. Pöhlmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, S" uniqKey="Liu S">S. Liu</name></author><author><name sortKey="Wu, S" uniqKey="Wu S">S. Wu</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fehr, A R" uniqKey="Fehr A">A.R. Fehr</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kirchdoerfer, R N" uniqKey="Kirchdoerfer R">R.N. Kirchdoerfer</name></author><author><name sortKey="Cottrell, C A" uniqKey="Cottrell C">C.A. Cottrell</name></author><author><name sortKey="Wang, N" uniqKey="Wang N">N. Wang</name></author><author><name sortKey="Pallesen, J" uniqKey="Pallesen J">J. Pallesen</name></author><author><name sortKey="Yassine, H M" uniqKey="Yassine H">H.M. Yassine</name></author><author><name sortKey="Turner, H L" uniqKey="Turner H">H.L. Turner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walls, A C" uniqKey="Walls A">A.C. Walls</name></author><author><name sortKey="Tortorici, M A" uniqKey="Tortorici M">M.A. Tortorici</name></author><author><name sortKey="Frenz, B" uniqKey="Frenz B">B. Frenz</name></author><author><name sortKey="Snijder, J" uniqKey="Snijder J">J. Snijder</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Rey, F A" uniqKey="Rey F">F.A. Rey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walls, A" uniqKey="Walls A">A. Walls</name></author><author><name sortKey="Tortorici, M A" uniqKey="Tortorici M">M.A. Tortorici</name></author><author><name sortKey="Bosch, B J" uniqKey="Bosch B">B.J. Bosch</name></author><author><name sortKey="Frenz, B" uniqKey="Frenz B">B. Frenz</name></author><author><name sortKey="Rottier, P J" uniqKey="Rottier P">P.J. Rottier</name></author><author><name sortKey="Dimaio, F" uniqKey="Dimaio F">F. DiMaio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, X" uniqKey="Gao X">X. Gao</name></author><author><name sortKey="Zhou, H" uniqKey="Zhou H">H. Zhou</name></author><author><name sortKey="Wu, C" uniqKey="Wu C">C. Wu</name></author><author><name sortKey="Xiao, Y" uniqKey="Xiao Y">Y. Xiao</name></author><author><name sortKey="Ren, L" uniqKey="Ren L">L. Ren</name></author><author><name sortKey="Paranhos Baccala, G" uniqKey="Paranhos Baccala G">G. Paranhos-Baccalà</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamaoka, Y" uniqKey="Yamaoka Y">Y. Yamaoka</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S. Matsuyama</name></author><author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S. Fukushi</name></author><author><name sortKey="Matsunaga, S" uniqKey="Matsunaga S">S. Matsunaga</name></author><author><name sortKey="Matsushima, Y" uniqKey="Matsushima Y">Y. Matsushima</name></author><author><name sortKey="Kuroyama, H" uniqKey="Kuroyama H">H. Kuroyama</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">Engineering (Beijing)</journal-id><journal-id journal-id-type="iso-abbrev">Engineering (Beijing)</journal-id><journal-title-group><journal-title>Engineering (Beijing, China)</journal-title></journal-title-group><issn pub-type="ppub">2095-8099</issn><issn pub-type="epub">2096-0026</issn><publisher><publisher-name>THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32288963</article-id><article-id pub-id-type="pmc">7104727</article-id><article-id pub-id-type="publisher-id">S2095-8099(18)30759-8</article-id><article-id pub-id-type="doi">10.1016/j.eng.2018.11.035</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins</article-title></title-group><contrib-group><contrib contrib-type="author" id="au005"><name><surname>Li</surname><given-names>Yan-Hua</given-names></name><xref rid="af005" ref-type="aff">a</xref><xref rid="af010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au010"><name><surname>Hu</surname><given-names>Chen-Yu</given-names></name><xref rid="af005" ref-type="aff">a</xref><xref rid="af010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au015"><name><surname>Wu</surname><given-names>Nan-Ping</given-names></name><xref rid="af005" ref-type="aff">a</xref><xref rid="af010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au020"><name><surname>Yao</surname><given-names>Hang-Ping</given-names></name><email>yaohangping@zju.edu.cn</email><xref rid="af005" ref-type="aff">a</xref><xref rid="af010" ref-type="aff">b</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author" id="au025"><name><surname>Li</surname><given-names>Lan-Juan</given-names></name><email>ljli@zju.edu.cn</email><xref rid="af005" ref-type="aff">a</xref><xref rid="af010" ref-type="aff">b</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="af005"><label>a</label>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China</aff><aff id="af010"><label>b</label>Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 31003, China</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding authors. <email>yaohangping@zju.edu.cn</email><email>ljli@zju.edu.cn</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>17</day><month>7</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>10</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>17</day><month>7</month><year>2019</year></pub-date><volume>5</volume><issue>5</issue><fpage>940</fpage><lpage>947</lpage><history><date date-type="received"><day>25</day><month>7</month><year>2018</year></date><date date-type="rev-recd"><day>24</day><month>10</month><year>2018</year></date><date date-type="accepted"><day>12</day><month>11</month><year>2018</year></date></history><permissions><copyright-statement>© 2019 THE AUTHORS</copyright-statement><copyright-year>2019</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="ab005"><p>Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a <italic>de novo</italic> coronavirus—MERS-CoV—that is associated with high mortality. However, the mechanism by which MERS-CoV infects humans remains unclear. To date, there is no effective vaccine or antibody for human immunity and treatment, other than the safety and tolerability of the fully human polyclonal Immunoglobulin G (IgG) antibody (SAB-301) as a putative therapeutic agent specific for MERS. Although rapid diagnostic and public health measures are currently being implemented, new cases of MERS-CoV infection are still being reported. Therefore, various effective measures should be taken to prevent the serious impact of similar epidemics in the future. Further investigation of the epidemiology and pathogenesis of the virus, as well as the development of effective therapeutic and prophylactic anti-MERS-CoV infections, is necessary. For this purpose, detailed information on MERS-CoV proteins is needed. In this review, we describe the major structural and nonstructural proteins of MERS-CoV and summarize different potential strategies for limiting the outbreak of MERS-CoV. The combination of computational biology and virology can accelerate the advanced design and development of effective peptide therapeutics against MERS-CoV. In summary, this review provides important information about the progress of the elimination of MERS, from prevention to treatment.</p></abstract><kwd-group id="kg005"><title>Keywords</title><kwd>MERS-CoV</kwd><kwd>Spike protein</kwd><kwd>Structural protein</kwd><kwd>Accessory protein</kwd><kwd>Nonstructural protein</kwd></kwd-group></article-meta></front><body><sec id="s0005"><label>1</label><title>Introduction</title><p id="p0005">Coronavirus (CoV) is an enveloped, positive, single-stranded RNA virus that causes mild upper respiratory infections in humans. Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a <italic>de novo</italic> coronavirus—MERS-CoV. MERS-CoV was originally isolated from an Arab patient who died of respiratory failure and renal failure in 2012, and was classified as a member of the CoV family, which is lineage C of the genus <italic>Betacoronavirus</italic>. From April 2012 to 22 May 2019, the total global number of laboratory-confirmed MERS cases reported to the World Health Organization (WHO) was 2428, with 838 associated deaths, or a fatality of about 35% (40.43% in Saudi Arabia) <xref rid="b0005" ref-type="bibr">[1]</xref>. Aside from MERS-CoV, only a few other CoVs are known to infect humans; these include human coronavirus (HCoV)-229E, HCoV-NL63, HKU1, and OC43, which usually result in relatively mild respiratory disease <xref rid="b0010" ref-type="bibr">[2]</xref>, <xref rid="b0015" ref-type="bibr">[3]</xref>. However, severe acute respiratory syndrome (SARS)-CoV and MERS-CoV are highly pathogenic and lead to high mortality, especially in the elderly and in immunocompromised patients <xref rid="b0020" ref-type="bibr">[4]</xref>, <xref rid="b0025" ref-type="bibr">[5]</xref>. MERS has broken out in 27 countries around the world, with major outbreaks occurring in Saudi Arabia, the United Arab Emirates, and Korea. The dromedary camel is the largest intermediate host for MERS-CoV, and bats are considered to be animal sources of MERS-CoV. However, the specific role of dromedaries in the transmission of the virus is not yet clear. To date, in addition to the safety and tolerability of the fully human polyclonal Immunoglobulin G (IgG) antibody (SAB-301), which is described as a putative therapeutic agent specific for MERS, no effective vaccines or antibodies have been reported for human immunization and therapy <xref rid="b0030" ref-type="bibr">[6]</xref>. Therefore, different intervention methods are need to treat MERS patients, including control of transmission. In this review, we describe the structure and potential functions of the reported MERS-CoV proteins, and discuss how their respective intervention strategies prevent virus transmission.</p></sec><sec id="s0010"><label>2</label><title>Structural proteins</title><p id="p0010">Many CoVs, including MERS-CoV, have a very large RNA genome of about 30 kb with at least ten predicted open reading frames (ORFs) <xref rid="b0015" ref-type="bibr">[3]</xref>, <xref rid="b0035" ref-type="bibr">[7]</xref>. The ORFs for the structural proteins are arranged as 5′-ORF1a/b-S-E-M-N-poly(A)-3′, which is a similar arrangement to that of other CoVs in lineage C of the genus <italic>Betacoronavirus</italic><xref rid="b0040" ref-type="bibr">[8]</xref>. Research has targeted these genes and their encoded proteins for use as vaccines, or for diagnostic or therapeutic purposes (<xref rid="t0005" ref-type="table">Table 1</xref>) <xref rid="b0045" ref-type="bibr">[9]</xref>, <xref rid="b0050" ref-type="bibr">[10]</xref>.<table-wrap position="float" id="t0005"><label>Table 1</label><caption><p>Structural proteins, genes, and their potential functions in MERS-CoV.</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Proteins</th><th>Coding genes</th><th>Functions and/or effect on the cellular response of the host</th></tr></thead><tbody><tr><td>Spike (S) protein</td><td>ORF2</td><td>Viral entry, receptor binding, membrane fusion</td></tr><tr><td>Envelope (E) protein</td><td>ORF6</td><td>Virion assembly; putative ion channel activity and is involved in viral budding and release; potential B cell epitopes</td></tr><tr><td>Membrane (M) protein</td><td>ORF7</td><td>Virion assembly—the formation of the viral envelope and viral core by interacting with the N protein; IFN antagonism</td></tr><tr><td>Nucleocapsid (N) protein</td><td>ORF8a</td><td>Main component of the nucleocapsid structure—essential for viral replication and assembly, and post-translational modification Modulating the host’s initial innate immune response</td></tr><tr><td>AP 3</td><td>ORF3</td><td>Viral replication and pathogenesis</td></tr><tr><td>AP 4a</td><td>ORF4a</td><td>Viral replication, IFN antagonism, protein kinase R (PKR) antagonism</td></tr><tr><td>AP 4b</td><td>ORF4b</td><td>IFN antagonism, nuclear factor kappa B (NF-κB) inhibition</td></tr><tr><td>AP 5</td><td>ORF5</td><td>IFN antagonist, modulation of NF-κB-mediated inflammation</td></tr><tr><td>Nsp1-coding region</td><td>nsp1</td><td>Specific recognition of viral RNA that is required for efficient viral replication; possibly interacts with cyclophilins and is thought to be a major virulence factor because it suppresses protein synthesis through the degradation of host mRNA</td></tr><tr><td>Papain-like protease (PLpro)</td><td>nsp3</td><td>PLpro is responsible for the cleavage at positions 1–3 to develop three nonstructural proteins (nsps); two selected sites (G720 and R911) were detected in the protease domain; viral replication; membrane proliferation; IFN antagonist; deubiquitination; putative dephosphorylation of Appr-1″-p, a side product of cellular tRNA splicing, to ADP-ribose</td></tr><tr><td>Transmembrane domain</td><td>nsp4</td><td>Viral replication; membrane proliferation</td></tr><tr><td>Main, chymotrypsin-like, or 3C-like protease (3CLpro)</td><td>nsp5</td><td>Viral survival—proteolytic processing of the replicative polyprotein at specific sites and 3CLpro cleaves the remaining positions 4–16 key functional enzymes, such as replicase and helicase</td></tr><tr><td>Transmembrane domain</td><td>nsp6</td><td>Membrane proliferation; interaction with nsp3 and nsp4</td></tr><tr><td>Primase</td><td>nsp8</td><td>Primase activity</td></tr><tr><td>Unknown</td><td>nsp9</td><td>Nsp9 is an essential protein dimer with RNA/DNA binding activity in SARS-CoV</td></tr><tr><td>Unknown</td><td>nsp10</td><td>Membrane proliferation—regulating 2′-<italic>O</italic>-MTase activity</td></tr><tr><td>RNA-dependent RNA polymerase</td><td>nsp12</td><td>Viral replication and transcription</td></tr><tr><td>Superfamily 1 helicase</td><td>nsp13</td><td>Viral replication; affects tropism and virulence</td></tr><tr><td>3′-to-5′exonuclease</td><td>nsp14</td><td>Viral replication—exoribonuclease activity</td></tr><tr><td>N7-methyltransferase Nidoviral endoribonuclease specific for U</td><td>nsp15</td><td>Viral replication—exoribonuclease activity</td></tr><tr><td><italic>S</italic>-adenosylmethionine-dependent ribose 2′-<italic>O</italic>-methyltransferase</td><td>nsp16</td><td>Methyltransferase inhibition; viral replication; IFN antagonism</td></tr></tbody></table></table-wrap></p><p id="p0015">Like other CoVs, MERS-CoV carries genes encoding accessory proteins (APs; 3, 4a, 4b, and 5), which antagonize host antiviral responses—typically type I interferon (IFN) responses—and contribute to virulence and pathogenesis. When expressed alone, CoV APs appear to interfere with the innate antiviral signaling pathway <xref rid="b0055" ref-type="bibr">[11]</xref>.</p><sec id="s0015"><label>2.1</label><title>Spike protein</title><p id="p0020">The spike (S) protein of MERS-CoV is a type I transmembrane glycoprotein that is expressed on the surface of the envelope of the virus and forms spikes from the virus body. The S protein comprises 1353 amino acids, is heavily glycosylated, and has a large extracellular domain and a short cytoplasmic terminal. S protein can be subdivided into S1 and S2, which have important effects in virus binding, fusion, and entry.</p><sec id="s0020"><label>2.1.1</label><title>Binding</title><p id="p0025">The S1 subunit has an N-terminal domain (NTD) and a receptor-binding domain (RBD), and comprises about 240 residues. MERS–RBD contains internal and external subdomains. The internal subdomains are relatively conserved among CoVs <xref rid="b0060" ref-type="bibr">[12]</xref>, whereas the structure of the external subdomains in CoVs varies greatly; the external subdomains mainly participate in receptor binding, resulting in the use of different receptors between CoVs. The RBD is responsible for the binding of dipeptidyl peptidase IV (DPP4, also known as human CD26). Interestingly, MERS-RBD can induce strong production of antibodies <italic>in vivo</italic>, which indicates that the S protein has a good immunogenicity for the induction of neutralizing antibodies (nAbs) <xref rid="b0065" ref-type="bibr">[13]</xref>, <xref rid="b0070" ref-type="bibr">[14]</xref>, <xref rid="b0075" ref-type="bibr">[15]</xref>, <xref rid="b0080" ref-type="bibr">[16]</xref>. The immunogenicity and protective potential of the NTD have been studied, and the recombinant N-terminal domain (rNTD) is a candidate vaccine against MERS <xref rid="b0085" ref-type="bibr">[17]</xref>.</p></sec><sec id="s0025"><label>2.1.2</label><title>Viral fusion</title><p id="p0030">There are two regions in the S2 subunit that participate in viral fusion—namely, heptapeptide repeats 1 and 2 (HR1 and HR2), which assemble into a typical six-helix bundle (also called the fusion core). Three HR2 chains in the HR1 side groove core emit three HR1 spirals, forming a central coiled spiral core that is a key membrane fusion structure <xref rid="b0090" ref-type="bibr">[18]</xref>, <xref rid="b0095" ref-type="bibr">[19]</xref>. Upon binding of S1 and DPP4, HR1 binds HR2 to form a temporary intermediate structure, causing the viral and cell membranes to move in close proximity to fuse the membranes.</p></sec><sec id="s0030"><label>2.1.3</label><title>Virus entry</title><p id="p0035">The S protein plays a key role in CoV tropism and morbidity, with proteolysis between S1 and S2 <xref rid="b0100" ref-type="bibr">[20]</xref>. There are many kinds of proteases (reviewed in Ref. <xref rid="b0105" ref-type="bibr">[21]</xref>) in hosts that can digest the S protein of MERS-CoV. For example, furin can be used in two steps by MERS-CoV in the activation process of cleavage during infection. First, furin recognizes the R751/S752 position and cleaves the S protein during biosynthesis. Next, S2 is further digested to S2′ at position R887/S888, which is adjacent to the fusion peptide after viral entry <xref rid="b0100" ref-type="bibr">[20]</xref>.</p></sec></sec><sec id="s0035"><label>2.2</label><title>Envelope protein</title><p id="p0040">The envelope (E) protein is an inner membrane protein that is also a small structural protein of MERS-CoV; it is 82 amino acids in length and is predicted to contain at least one transmembrane helix <xref rid="b0110" ref-type="bibr">[22]</xref>. The E protein of CoVs plays an important role in intracellular trafficking, host recognition, viral assembly, and virus budding <xref rid="b0110" ref-type="bibr">[22]</xref>. However, the exact function of the CoV E protein during infection remains unclear.</p><sec id="s0040"><label>2.2.1</label><title>Virion assembly</title><p id="p0045">Researchers have used infectious bronchitis virus (IBV) infection to prove that the E protein is required for virion assembly, and that its other role is disturbing the secretory pathway <xref rid="b0115" ref-type="bibr">[23]</xref>. The MERS-CoV E protein has a single hydrophobic domain (HD) that targets the Golgi composite membrane and has cationic channel activity <italic>in vitro</italic>. The purified MERS-CoV E proteins form pentameric ion channels in the lipid bilayer. Lack of the E protein may lead to elimination of channel activity. Based on the proposed channel activity as a virulence factor, the MERS-CoV E protein is a potential antiviral therapeutic target <xref rid="b0110" ref-type="bibr">[22]</xref>.</p></sec><sec id="s0045"><label>2.2.2</label><title>B cell epitopes</title><p id="p0050">Researchers have used software or programs such as LaserGene (DNASTAR, Inc., USA), PHYRE 2 (Structural Bioinformatics Group, Imperial College London, UK), and PyMOL (Schrödinger, LLC, USA) to identify a potential B epitope with high antigenicity at positions 58–82 of the E protein <xref rid="b0120" ref-type="bibr">[24]</xref>.</p></sec></sec><sec id="s0050"><label>2.3</label><title>Membrane protein</title><p id="p0055">The membrane (M) protein is important in viral assembly, the formation of the viral envelope, and the formation of the viral core by interacting with the nucleocapsid (N) protein <xref rid="b0125" ref-type="bibr">[25]</xref>, <xref rid="b0130" ref-type="bibr">[26]</xref>. Therefore, the development of fusion peptides and IFN antagonists may be an important treatment option.</p></sec><sec id="s0055"><label>2.4</label><title>Nucleocapsid protein</title><p id="p0060">The N protein of MERS-CoV is a phosphorylated basic protein and is the second largest structural protein, containing 413 amino acid residues. The N protein binds to the RNA genome to form a nucleocapsid, which is important in virus replication and assembly <xref rid="b0135" ref-type="bibr">[27]</xref>.</p><sec id="s0060"><label>2.4.1</label><title>Virion replication and assembly</title><p id="p0065">The N-terminus of the N protein (residues 39–165) may be the RNA-binding region, and the C-terminus may be a self-binding oligomer-forming region <xref rid="b0140" ref-type="bibr">[28]</xref>. A comparison of homology between MERS-CoV and other CoVs shows that although the N protein has low homology over the entire amino acid sequence, certain local amino acid sequences—especially the N-terminal amino acid sequence—are highly conserved. The SARS-CoV N protein can increase replication by overexpression <xref rid="b0145" ref-type="bibr">[29]</xref>. The nucleocapsid structure not only requires the recognition of the characteristic sequences of the viral RNA, but also must recognize binding to other structural viral proteins. After the N protein forms a complex with the viral genomic RNA, the RNA is protected from destruction by nucleases in the host cell <xref rid="b0150" ref-type="bibr">[30]</xref>. X-ray diffraction measurement at very high resolution (2.4 Å) was used to discover an intrinsically disordered region (IDR) and an NTD at the N-terminus of the N protein. This model shows that the NTDs in CoVs are relatively conserved <xref rid="b0155" ref-type="bibr">[31]</xref>.</p></sec><sec id="s0065"><label>2.4.2</label><title>Post-translational modification</title><p id="p0070">The N proteins of SARS-CoV and MERS-CoV are ADP-ribosylated, which is a common post-translational modification; however, it is unclear how this regulates RNA virus infection. In a study that screened for ADP-ribosylating proteins after infection with CoV, researchers identified an ADP-ribosylated protein of about 55 kDa <italic>in vivo</italic>, which was subsequently verified as a CoV N protein. Therefore, CoV N proteins may modulate the post-translational modification of certain important proteins <xref rid="b0150" ref-type="bibr">[30]</xref>.</p></sec><sec id="s0070"><label>2.4.3</label><title>Modulation of the innate immune response</title><p id="p0075">The N protein of CoV may inhibit type I IFN production by interfering with the interaction between the triple motif protein 25 (TRIM25) and retinoic acid-inducible gene I (RIG-I), and by binding to the E3 ubiquitin ligase of TRIM25. Thus, inhibiting the ubiquitination and activation of RIG-I mediated by TRIM25 ultimately leads to the inhibition of IFN production, suggesting that the N protein of a CoV regulates the host’s immune response against the virus <xref rid="b0145" ref-type="bibr">[29]</xref>.</p><p id="p0080">The MERS-CoV N protein is thought to interact with mannose-associated serine protease 2 (MASP2) <xref rid="b0160" ref-type="bibr">[32]</xref> and translation elongation factor 1 (EF-1A) <xref rid="b0165" ref-type="bibr">[33]</xref> in the host. Once the mannose-binding lectin recognizes the mannan on the surface of the virus-infected cell, it recruits MASP2 and then activates its enzymatic activity, eventually causing a local or systemic inflammatory response. EF-1A acts as a translation elongation factor, and catalyzes the aminoacyl-tRNA to the A site in the ribosome. EF-1A can play a regulatory role in the assembly of the cytoskeleton, microfilaments, and cytokinesis rings. The interaction between the MERS-CoV N protein and EF-1A disrupts the formation of cytokinesis loops and inhibits lymphocyte proliferation, which may explain the reduction in the number of lymphocytes in patients with MERS.</p></sec></sec></sec><sec id="s0075"><label>3</label><title>Accessory proteins</title><p id="p0085">MERS-CoV has a large number of genomes encoding a variety of APs (dORF: ORF3, ORF4a, ORF4b, ORF5). Even among closely related CoVs, their number and sequence are different, and lead to host shift and HCoV emergence <xref rid="b0170" ref-type="bibr">[34]</xref>.</p><sec id="s0080"><label>3.1</label><title>Viral replication</title><p id="p0090">The MERS-CoV AP ORF is important for the replication of the virus <italic>in vivo</italic> and <italic>in vitro</italic>, which allows these ORFs to be used as targets of vaccine production, and emphasizes that MERS-CoV APs are potential targets for monitoring and therapeutic treatment. In addition, parallel disruption of the AP ORF provides a rapid response platform for new mutations of SARS or MERS-CoV AP ORFs <xref rid="b0175" ref-type="bibr">[35]</xref>.</p></sec><sec id="s0085"><label>3.2</label><title>Dysregulating host responses</title><p id="p0095">The APs of MERS-CoV may invoke a hostile response through different modes, including IFN antagonism and the protein kinase R (PKR) and nuclear factor kappa B (NF-κB) pathways.</p><sec id="s0090"><label>3.2.1</label><title>IFN antagonism</title><p id="p0100">The attenuated function of dORF3-5 mutants is mainly caused by host-response disorders, including disrupted cellular processes and strong inflammation. ORF4-5 proteins increase IFN pathway activation and are potent IFN antagonists. They can inhibit IFN production (e.g., IRF-3/7) and interferon stimulated response element (ISRE) signaling pathways. The MERS-CoV ORF4a protein most likely interferes with the anti-antiviral effects of IFNs <xref rid="b0180" ref-type="bibr">[36]</xref>.</p><p id="p0105">IFN antagonism is a key element of viral pathogenesis. The IFN-inducible oligoadenylate synthase (OAS)-RNase L pathway is activated after the sensing of viral double-stranded RNA (dsRNA); thus, the virus and single-stranded RNA (ssRNA) of the host are cleaved, which hinders the replication and spread of the virus. ORF4b, which is mainly located in the nucleus (while all the other proteins are located in the cytoplasm), has phosphodiesterase (PDE) activity and activates RNase L. Treatment with NS4b interferes with the pathogenesis of MERS-CoV in <italic>in vivo</italic> models <xref rid="b0185" ref-type="bibr">[37]</xref>.</p></sec><sec id="s0095"><label>3.2.2</label><title>PKR antagonism</title><p id="p0110">The p4a of MERS-CoV is essential for PKR antagonistic activity. To establish infection and spread, MERS-CoV must regulate a complex antiviral host-response network (type I IFN (IFN-α/β) responses). Phosphorylation of eIF2α by PKR leads to inhibition of the translation of cells and viruses, and the formation of stress granules (SGs), which provide platforms for antiviral signaling pathways <xref rid="b0190" ref-type="bibr">[38]</xref>.</p></sec><sec id="s0100"><label>3.2.3</label><title>NF-κB inhibition</title><p id="p0115">MERS-CoV 4b needs to prevent a strong host-dependent reaction during infection. During viral infection, 4b acts to interfere with NF-κB-mediated innate immune responses by binding NF-κB to nuclear transcription factor-α4 (KPNA4) and translocating it to the nucleus to play a competitive role <xref rid="b0100" ref-type="bibr">[20]</xref>. ORF5 also has some effect on the regulation of NF-κB-mediated inflammation <xref rid="b0175" ref-type="bibr">[35]</xref>.</p></sec></sec></sec><sec id="s0105"><label>4</label><title>Nonstructural proteins</title><p id="p0120">ORF1a and ORF1b at the 5′-terminus of the CoV genome encode polyprotein 1a and polyprotein 1b, which may cleaved into 16 nonstructural proteins (nsps). These proteins are essential for viral replication and transcription <xref rid="b0195" ref-type="bibr">[39]</xref>.</p><sec id="s0110"><label>4.1</label><title>Proteolysis</title><p id="p0125">MERS-CoV 3C-like protease (3CLpro) and papain-like protease (PLpro) are affected by the different genetic and evolutionary effects of protein sequence formation, codon usage patterns, and codon usage bias. The cleavage points of PLpro are positions 1–3, which produces three nsps, while 3CLpro cleavage occur at the remaining positions 4–16. Nsp3 (∼200 kDa) is a multifunctional protein that contains up to 16 different domains and regions, and is associated with viral RNA, nucleocapsid proteins, and other viral proteins involved in polyprotein processing. The PLpro activity of nsp3 is the established target of new antiviral drugs <xref rid="b0200" ref-type="bibr">[40]</xref>. PLpro is controlled by a wide range of components, mutations, and other effects. Antiviral drugs, such as PLpro inhibitors and 3CLpro inhibitors (<xref rid="t0010" ref-type="table">Table 2</xref>), have been studied for their innate immunosuppression profiles <xref rid="b0205" ref-type="bibr">[41]</xref>, <xref rid="b0210" ref-type="bibr">[42]</xref>. Nsp5 is widely involved in virus-encoded polyproteins (ppla, pplab) and 16 nsps processing; therefore, nsp5 is essential and indispensable for virus survival. In addition, the lack of cell homologs of human nsp5 makes it an ideal target for antiviral drug design <xref rid="b0215" ref-type="bibr">[43]</xref>. The adaptive evolution of nsp3 in MERS-CoV strains is ongoing. CoV nsp3 can be used as a primary screening target, and nsp3 sequencing should be considered for monitoring and site-specific investigations <xref rid="b0220" ref-type="bibr">[44]</xref>.<table-wrap position="float" id="t0010"><label>Table 2</label><caption><p>Summary of potential products targeting MERS-CoV proteins.</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Therapeutic products</th><th>Targets</th><th><italic>In vivo/in vitro</italic></th><th>Safety/advantages</th></tr></thead><tbody><tr><td>Mersmab</td><td>S1 RBD</td><td><italic>In vitro</italic></td><td>—</td></tr><tr><td>m336, m337, m338</td><td>S1 RBD</td><td><italic>In vitro/in vivo</italic> (mouse, rabbit-m336)</td><td>—</td></tr><tr><td>MERS-4, MERS-27</td><td>S1 RBD</td><td><italic>In vitro</italic></td><td>—</td></tr><tr><td>4C2</td><td>S1 RBD</td><td><italic>In vitro/in vivo</italic> (mouse)</td><td>Prophylactic and therapeutic</td></tr><tr><td>hMS-1</td><td>S1 RBD</td><td><italic>In vitro/in vivo</italic> (mouse)</td><td>—</td></tr><tr><td>LCA60</td><td>S1 RBD</td><td><italic>In vitro/in vivo</italic> (mouse)</td><td>Targets both NTD and RBD, stable Chinese hamster ovary (CHO) cell line, prophylactic and therapeutic</td></tr><tr><td>3B11-N</td><td>S1 RBD</td><td><italic>In vitro/in vivo</italic> (rhesus monkeys)</td><td>Prophylactic</td></tr><tr><td>2F9, 1F7, YS110</td><td>Human-anti-DPP4</td><td><italic>In vitro</italic></td><td>—</td></tr><tr><td>1E9, IF8, 3A1</td><td>S1 RBD</td><td><italic>In vitro</italic></td><td>—</td></tr><tr><td>3B12, 3C12, 3B11, M14D3</td><td>S1 RBD</td><td><italic>In vitro</italic></td><td>—</td></tr><tr><td>RBD s377-588-Fc IgG fusion</td><td>RBD-IgG fusion</td><td><italic>In vitro/in vivo</italic> (mouse)</td><td>Humoral response in mice; potential intranasal administration; improved by adjuvant MF59; divergent strains/escape mutants</td></tr><tr><td>G4</td><td>S1 RBD</td><td><italic>In vitro</italic></td><td>—</td></tr><tr><td>Full-length S protein proprietary nanoparticles</td><td>S protein</td><td><italic>In vitro/in vivo</italic> (mouse)</td><td>Use of adjuvants improves humoral response</td></tr><tr><td>MVA expressing full-length S protein</td><td>S protein</td><td><italic>In vitro/in vivo</italic> (mouse, camel)</td><td>T cell and humoral response; entering human clinical trials; potential for veterinary use with camels</td></tr><tr><td>Ad5 or ad41 adenovirus expressing full-length S protein</td><td>S protein</td><td><italic>In vitro/in vivo</italic> (mouse)</td><td>T cell and neutralizing antibody responses</td></tr><tr><td>Measles virus expressing full-length S protein (vaccine candidate)</td><td>S protein</td><td><italic>In vitro/in vivo</italic> (mouse)</td><td>T cell and neutralizing antibody responses</td></tr><tr><td>GLS-5300 plasmid vaccine</td><td>S protein</td><td><italic>In vitro/in vivo</italic> (mouse, camels, and macaques), human clinical trials</td><td>T cell and neutralizing antibody responses; in a phase I clinical trial</td></tr><tr><td>MERS-GD27 and MERS-GD33</td><td>S protein</td><td><italic>In vitro</italic></td><td>Receptor-binding site and the effect of synergism in neutralizing MERS-CoV</td></tr><tr><td>HR2P</td><td>Anti-HR2</td><td><italic>In vitro</italic></td><td>—</td></tr><tr><td>HR2P-M2</td><td>Anti-HR2</td><td><italic>In vitro/in vivo</italic> (mouse)</td><td>Blocks 6 HB bundle formation; enhances IFN-β effect; potential intranasal treatments</td></tr><tr><td>IFNs</td><td>IFN antagonists</td><td><italic>In vitro/in vivo</italic></td><td>Combination therapy allows reduced amounts of each IFN</td></tr><tr><td>Camostat</td><td>TMPRSS2 inhibitor</td><td><italic>In vivo</italic> (mouse), SARS-CoV</td><td>Already in clinical use (chronic pancreatitis)</td></tr><tr><td>Nafamostat</td><td>TMPRSS2 inhibitor</td><td>Split-protein-based cell–cell fusion assay</td><td>Already in clinical use (anti-coagulant)</td></tr><tr><td>Teicoplanin dalbavancin oritavancin telavancin</td><td>Cathepsin L inhibitor</td><td>High-throughput screening</td><td>Already in clinical use (antibiotic Gram-positive bacterial infections)</td></tr><tr><td>6-mercaptopurine (6MP)</td><td rowspan="2">PLpro inhibitor</td><td rowspan="2"><italic>In vitro</italic></td><td rowspan="2">Potential for more MERS-specific agents</td></tr><tr><td>6-thioguanine (6TG)</td></tr><tr><td>F2124-0890</td><td>PLpro inhibitor</td><td><italic>In vitro</italic></td><td>—</td></tr><tr><td>Lopinaivor</td><td>Mpro</td><td><italic>In vitro/in vivo</italic> (marmosets)</td><td>High activity in low micromolar range <italic>in vitro</italic>; better outcomes, reduced mortality in marmosets</td></tr></tbody></table></table-wrap></p></sec><sec id="s0115"><label>4.2</label><title>Viral replication</title><p id="p0130">CoV RNA synthesis is associated with replication organelles (ROs) composed of a modified endoplasmic reticulum (ER) membrane. These are converted to double-membrane vesicles (DMVs) containing viral dsRNA and then converted to other crimped membranes, which together form a reticulovesicular network. Nsp3, 4, and 6 of SARS-CoV contain transmembrane domains and are all responsible for the formation of DMVs <xref rid="b0225" ref-type="bibr">[45]</xref>. In addition, the cis-acting element at the 5′ end of the nsp1 coding region facilitates the specific recognition of viral RNA, which is necessary for efficient virus replication <xref rid="b0230" ref-type="bibr">[46]</xref>.</p><p id="p0135">MERS-CoV helicase (nsp13) is one of the most important viral replication enzymes and can profoundly affect tropism and virulence <xref rid="b0235" ref-type="bibr">[47]</xref>. Nsp13 unfolds DNA and RNA in the 5′ to 3′ direction and is a kinematic protein that catalyzes the progressive separation of double-stranded nucleic acids into two single-stranded nucleic acids, using energy generated by ATP hydrolysis. Therefore, the nsp13 helicase can be used as a therapeutic target to inhibit the replication of MERS-CoV <xref rid="b0240" ref-type="bibr">[48]</xref>. In addition, nsp8 has major activity in viral replication; nsp12 (RNA-dependent RNA polymerase (RdRp)) plays a role in virus replication and transcription and can be used as a diagnostic (RdRpSeq assay) and as an antiviral target (polymerase inhibitor); nsp14 has exoribonuclease activity; and nsp15 has endoribonuclease activity, and can effectively prevent the activation of dsRNA sensor (including melanoma differentiation-related protein 5 (Mda5), OAS, and PKR) in host cells <xref rid="b0045" ref-type="bibr">[9]</xref>, <xref rid="b0245" ref-type="bibr">[49]</xref>, <xref rid="b0250" ref-type="bibr">[50]</xref>.</p></sec><sec id="s0120"><label>4.3</label><title>Methyltransferase inhibition</title><p id="p0140">Nsp16 is an <italic>S</italic>-adenosine-<italic>L</italic>-methionine (SAM)-dependent 2′-<italic>O</italic>-methyltransferase (2′-<italic>O</italic>-MTase), and nsp10 plays an important role in regulating 2′-<italic>O</italic>-MTase activity. SAM binding can promote the assembly of the nsp10/nsp16 complex, which enzymatically converts 7mGpppG (cap-0) to 7mGpppG2′Om (cap-1) RNA in a SAM-dependent manner through 2′-OH methylation of SAM. Alanine mutagenesis has been used to identify the nsp16 residues that affect RNA recognition. The balance of SAM/<italic>S</italic>-adenosyl-<italic>L</italic>-homocysteine (SAH) can regulate 2′-<italic>O</italic>-methyltransferase activity, which increases SAH hydrolase inhibition and can interfere with CoV replication cycles <xref rid="b0255" ref-type="bibr">[51]</xref>.</p></sec><sec id="s0125"><label>4.4</label><title>Membrane proliferation</title><p id="p0145">Working together, nsp3 and nsp4 exert their effects in pairing membranes. Nsp6 can promote membrane proliferation by forming perinuclear vesicles, which is thought to require full-length nsp3, because no DMVs are seen in cells co-expressing C-terminally truncated nsp3 with nsp4 and nsp6 <xref rid="b0260" ref-type="bibr">[52]</xref>.</p></sec><sec id="s0130"><label>4.5</label><title>Interaction with the host</title><sec id="s0135"><label>4.5.1</label><title>IFN antagonism</title><p id="p0150">Most adaptive events occur through nsp3, which inhibits the IFN response via its deubiquitination and de-esterification activity <xref rid="b0205" ref-type="bibr">[41]</xref>. Nsp3 is currently undergoing selection, based on MERS-CoV that has been isolated from humans and camels <xref rid="b0220" ref-type="bibr">[44]</xref>. Positive selection changes in nsp3 (R911C) were observed in human-only viruses, suggesting that virus adaptation in humans represents a potential selective pressure <xref rid="b0220" ref-type="bibr">[44]</xref>. Nsp16 helps the virus to escape from cellular innate immunity and uses IFN-induced protein with tetratricopeptide repeats 1 (IFIT-1) protein to inhibit viral translation <xref rid="b0170" ref-type="bibr">[34]</xref>. Using reverse genetics, dnsp16-mutated MERS-CoV showed attenuation based on type I IFN; the mutation was partially recovered in the absence of IFIT-1 <xref rid="b0265" ref-type="bibr">[53]</xref>.</p></sec><sec id="s0140"><label>4.5.2</label><title>Deubiquitination</title><p id="p0155">PLpro’s ubiquitin-like domain (Ubl) becomes fully flexible after binding to ubiquitin, and its increased flexibility is important for its interaction with other downstream proteins and for inhibition of innate immunity <xref rid="b0270" ref-type="bibr">[54]</xref>. The four major residues involved in deubiquitination-L106, R168, P163, and F265 are conserved in all MERS-CoVs, but differ from other betacoronaviruses. Thus, downregulation of the deubiquitination of nsp3 may lead to a weakened interaction between MERS-CoV and the host immune system <xref rid="b0270" ref-type="bibr">[54]</xref>, <xref rid="b0275" ref-type="bibr">[55]</xref>.</p></sec><sec id="s0145"><label>4.5.3</label><title>Inhibition of the expression and translation of host mRNA</title><p id="p0160">Nsp1 inhibits the host innate immune response by binding to dsRNA and cell double-stranded DNA; therefore, it is considered to be the best checkpoint of viral invasion <xref rid="b0280" ref-type="bibr">[56]</xref>. At the same time, the C-terminus of nsp1 targets TNF receptor-associated factor 3 (TRAF-3) to inhibit the production of IFN-β <xref rid="b0285" ref-type="bibr">[57]</xref>. In addition, activation of interferon-regulated transcription factor 3 (IRF3) <xref rid="b0290" ref-type="bibr">[58]</xref> and PKR can be inhibited by other nsp1 domains <xref rid="b0295" ref-type="bibr">[59]</xref>. Nsp1 of CoV may also interact with cyclophilin, and is considered to be a major virulence factor because it degrades host mRNA. The mRNA degradation activity of MERS-CoV nsp1 is separate from its translational inhibitory function. Furthermore, certain residues of MERS-CoV nsp1 are crucial for evading translational shutdown <xref rid="b0230" ref-type="bibr">[46]</xref>. The escape of MERS-CoV mRNAs from inhibition by MERS-CoV nsp1 is promoted by their cytoplasmic origin <xref rid="b0300" ref-type="bibr">[60]</xref>.</p></sec></sec></sec><sec id="s0150"><label>5</label><title>Potential strategies to treat MERS</title><p id="p0165">There is no completely effective treatment for MERS-CoV. Current treatment methods mainly imitate the treatment of SARS-CoV, and comprise the following: symptomatic treatment, including biological therapy such as monoclonal antibodies (mAbs), blockers, protease inhibitors, corticosteroids, and IFN; chemical drugs, such as Acyclovir <xref rid="b0305" ref-type="bibr">[61]</xref>, chlorpromazine hydrochloride <xref rid="b0310" ref-type="bibr">[62]</xref>, loperamide, and lopinavir <xref rid="b0315" ref-type="bibr">[63]</xref>; broad-spectrum antibiotics, such as ribavirin, lopinavir-ritonavir, or mycophenolate mofetil <xref rid="b0320" ref-type="bibr">[64]</xref>; and nanoparticle vaccines <xref rid="b0325" ref-type="bibr">[65]</xref>. However, well-organized clinical trials have not yet been carried out. Therefore, we analyzed potential prevention and treatment methods from the perspective of their molecular characteristics, which provides a reference for the development of effective and targeted prevention and treatment, and especially of biological strategies.</p><sec id="s0155"><label>5.1</label><title>Strategies related to the S protein</title><sec id="s0160"><label>5.1.1</label><title>Antibodies toward S protein</title><p id="p0170">The mAbs are regarded as a potential intervention method and have been used to diagnose many diseases. The main products are shown in <xref rid="t0010" ref-type="table">Table 2</xref>. LCA60 is the only antibody isolated from recovered MERS patients. Preclinical development of this product has been completed, and good manufacturing practices (GMP)-approved cell lines that express high concentrations of purified and highly efficient antibodies have been established <xref rid="b0330" ref-type="bibr">[66]</xref>. Studies of human nAbs <xref rid="b0335" ref-type="bibr">[67]</xref> and mAbs <xref rid="b0340" ref-type="bibr">[68]</xref>, <xref rid="b0345" ref-type="bibr">[69]</xref> have been performed. These antibody-based drugs are specific and effective inhibitors of RBD, and show strong resistance to MERS-CoV-neutralizing activity. <xref rid="t0010" ref-type="table">Table 2</xref> describes other studies on potential antibodies and mAbs. Potential antibodies REGN3051 and REGN3048 have demonstrated effective prophylaxis in MERS-CoV-infected animal models <xref rid="b0350" ref-type="bibr">[70]</xref>, <xref rid="b0355" ref-type="bibr">[71]</xref>, as have the following treatments: Mersmab <xref rid="b0360" ref-type="bibr">[72]</xref>; 1E9, IF8, 3A1, 2F9, 1F7, and YS110 <xref rid="b0365" ref-type="bibr">[73]</xref>; hMs-1 <xref rid="b0370" ref-type="bibr">[74]</xref>; 4C2 <xref rid="b0375" ref-type="bibr">[75]</xref>; and RBD s377-588-Fc IgG fusion <xref rid="b0380" ref-type="bibr">[76]</xref>. G4 recognizes the variable glycosylation loops in CoVs that define the four conformational states of the trimer. These studies may contribute to our understanding of fusion initiation and provide a basis for the design of structure-based CoV vaccines <xref rid="b0025" ref-type="bibr">[5]</xref>, <xref rid="b0385" ref-type="bibr">[77]</xref>.</p></sec><sec id="s0165"><label>5.1.2</label><title>Inhibitors</title><p id="p0175">MERS-CoV SP is essential for the virus to enter cells; therefore, other therapeutic agents that blockade viral cell membrane fusion should be exploited, such as feline protein inhibitors <xref rid="b0390" ref-type="bibr">[78]</xref>, TMPRSS2 inhibitors <xref rid="b0395" ref-type="bibr">[79]</xref>, PLpro inhibitors <xref rid="b0205" ref-type="bibr">[41]</xref>, furin inhibitors <xref rid="b0400" ref-type="bibr">[80]</xref>, kinase inhibitors <xref rid="b0405" ref-type="bibr">[81]</xref>, and IFN-induced transmembrane (IFITM) proteins <xref rid="b0410" ref-type="bibr">[82]</xref>.</p></sec><sec id="s0170"><label>5.1.3</label><title>Peptides</title><p id="p0180">HR1P at position 998–1038 and HR2P at positions 1251–1286 have been identified by Lu et al. <xref rid="b0095" ref-type="bibr">[19]</xref> and Liu et al. <xref rid="b0415" ref-type="bibr">[83]</xref> as being responsible for the formation of the fusion core. The HR2P peptide can inhibit viral replication of MERS-CoV in cell lines, such as Calu-3 and HFL <xref rid="b0095" ref-type="bibr">[19]</xref>. HR2P plays a role in the inhibition of the replication of MERS-CoV and its stimulatory fusion. Although there is little knowledge concerning assembly and release, inhibiting these viral processes may be an important goal in the future <xref rid="b0320" ref-type="bibr">[64]</xref>, <xref rid="b0420" ref-type="bibr">[84]</xref></p></sec><sec id="s0175"><label>5.1.4</label><title>Potential therapeutic components</title><p id="p0185">Low-temperature electron microscopy recently revealed a global pre-fusional structure of the full-length S-exodomain, indicating that the NTD and C terminal domain (CTD) form a “V” shape that helps the overall S trimer’s triangular appearance <xref rid="b0425" ref-type="bibr">[85]</xref>, <xref rid="b0430" ref-type="bibr">[86]</xref>, <xref rid="b0435" ref-type="bibr">[87]</xref>. The S2 subunit is linked to the viral membrane and is characterized by the presence of a long alpha helix. This structural information could form the basis for the structure-based immunogen design of vaccines against betacoronaviruses. The combination of computational biology and virology could accelerate advanced designs of agents acting against MERS-CoV, resulting in higher efficacy <xref rid="b0320" ref-type="bibr">[64]</xref>.</p></sec></sec><sec id="s0180"><label>5.2</label><title>Strategies related to the N protein</title><p id="p0190">The N protein of MERS-CoV is abundantly produced during infection and shows strong immunogenicity, indicating that it is an ideal antigen for virus antibody detection. Anti-N IgG can be used as an indicator of susceptibility to human CoV infection <xref rid="b0440" ref-type="bibr">[88]</xref>. Reports have described new methods to generate mAbs directed against N proteins. Using the wheat germ cell protein synthesis system, a large number of MERS-CoV N protein antigens were successfully prepared in a highly soluble and intact immune state <xref rid="b0445" ref-type="bibr">[89]</xref>.</p></sec><sec id="s0185"><label>5.3</label><title>Potential strategies to treat MERS-CoV based on its characteristics</title><p id="p0195">Given the biological characteristics of MERS-CoV, infection prevention and control measures are critical to prevent the possible spread of this virus. For patients with MERS, effective early diagnosis and early treatment are difficult to achieve, mainly because of atypical early symptoms, the limitations of detection methods, and airborne transmission. Therefore, regardless of the diagnosis, healthcare providers should always take consistent standard precautions for all patients. IgM-type antibodies against MERS-CoV proteins need to be detected more effectively, necessitating the development of more effective antibodies.</p></sec></sec><sec id="s0190"><label>6</label><title>Conclusion</title><p id="p0200">Explosive epidemics of MERS-CoV pose a serious threat to global public health and emphasize the need to further investigate the epidemiology and pathogenesis of this virus, in addition to developing effective therapeutic and preventive drugs against MERS-CoV infection. Despite rapid advances in diagnostics and public health measures, new MERS-CoV cases are still being reported. This suggests that multiple interventions targeting different affected populations may be necessary to stop these outbreaks. As described herein, the structural information associated with the MERS-CoV proteins may be used to develop different potential interventions to limit the outbreak of MERS-CoV. There is a need to better understand the pathogenesis of MERS-CoV in order to identify viral and host factors that play an important role in the development of MERS in humans; this may provide potentially novel therapeutic and intervention options.</p></sec></body><back><ref-list id="bi005"><title>References</title><ref id="b0005"><label>1</label><element-citation publication-type="journal" id="h0005"><person-group person-group-type="author"><name><surname>Hui</surname><given-names>D.S.</given-names></name><name><surname>Azhar</surname><given-names>E.I.</given-names></name><name><surname>Kim</surname><given-names>Y.J.</given-names></name><name><surname>Memish</surname><given-names>Z.A.</given-names></name><name><surname>Oh</surname><given-names>M.D.</given-names></name><name><surname>Zumla</surname><given-names>A.</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission</article-title><source>Lancet Infect Dis</source><volume>18</volume><issue>8</issue><year>2018</year><fpage>e217</fpage><lpage>e227</lpage><pub-id pub-id-type="pmid">29680581</pub-id></element-citation></ref><ref id="b0010"><label>2</label><element-citation publication-type="journal" id="h0010"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>H.</given-names></name><name><surname>Lei</surname><given-names>H.</given-names></name><name><surname>Santarsiero</surname><given-names>B.D.</given-names></name><name><surname>Gatuz</surname><given-names>J.L.</given-names></name><name><surname>Cao</surname><given-names>S.</given-names></name><name><surname>Rice</surname><given-names>A.J.</given-names></name></person-group><article-title>Inhibitor recognition specificity of MERS-CoV papain-like protease may differ from that of SARS-CoV</article-title><source>ACS Chem Biol</source><volume>10</volume><issue>6</issue><year>2015</year><fpage>1456</fpage><lpage>1465</lpage><pub-id pub-id-type="pmid">25746232</pub-id></element-citation></ref><ref id="b0015"><label>3</label><element-citation publication-type="journal" id="h0015"><person-group person-group-type="author"><name><surname>Choi</surname><given-names>J.</given-names></name><name><surname>Kim</surname><given-names>M.G.</given-names></name><name><surname>Oh</surname><given-names>Y.K.</given-names></name><name><surname>Kim</surname><given-names>Y.B.</given-names></name></person-group><article-title>Progress of Middle East respiratory syndrome coronavirus vaccines: a patent review</article-title><source>Expert Opin Ther Pat</source><volume>27</volume><issue>6</issue><year>2017</year><fpage>721</fpage><lpage>731</lpage><pub-id pub-id-type="pmid">28121202</pub-id></element-citation></ref><ref id="b0020"><label>4</label><element-citation publication-type="journal" id="h0020"><person-group person-group-type="author"><name><surname>Zaki</surname><given-names>A.M.</given-names></name><name><surname>Van Boheemen</surname><given-names>S.</given-names></name><name><surname>Bestebroer</surname><given-names>T.M.</given-names></name><name><surname>Osterhaus</surname><given-names>A.D.</given-names></name><name><surname>Fouchier</surname><given-names>R.A.</given-names></name></person-group><article-title>Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia</article-title><source>N Engl J Med</source><volume>367</volume><issue>19</issue><year>2012</year><fpage>1814</fpage><lpage>1820</lpage><pub-id pub-id-type="pmid">23075143</pub-id></element-citation></ref><ref id="b0025"><label>5</label><element-citation publication-type="journal" id="h0025"><person-group person-group-type="author"><name><surname>Pallesen</surname><given-names>J.</given-names></name><name><surname>Wang</surname><given-names>N.</given-names></name><name><surname>Corbett</surname><given-names>K.S.</given-names></name><name><surname>Wrapp</surname><given-names>D.</given-names></name><name><surname>Kirchdoerfer</surname><given-names>R.N.</given-names></name><name><surname>Turner</surname><given-names>H.L.</given-names></name></person-group><article-title>Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen</article-title><source>Proc Natl Acad Sci USA</source><volume>114</volume><issue>35</issue><year>2017</year><fpage>E7348</fpage><lpage>E7357</lpage><pub-id pub-id-type="pmid">28807998</pub-id></element-citation></ref><ref id="b0030"><label>6</label><element-citation publication-type="journal" id="h0030"><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></person-group><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><issue>4</issue><year>2018</year><fpage>410</fpage><lpage>418</lpage><pub-id pub-id-type="pmid">29329957</pub-id></element-citation></ref><ref id="b0035"><label>7</label><element-citation publication-type="journal" id="h0035"><person-group person-group-type="author"><name><surname>Van Boheemen</surname><given-names>S.</given-names></name><name><surname>De Graaf</surname><given-names>M.</given-names></name><name><surname>Lauber</surname><given-names>C.</given-names></name><name><surname>Bestebroer</surname><given-names>T.M.</given-names></name><name><surname>Raj</surname><given-names>V.S.</given-names></name><name><surname>Zaki</surname><given-names>A.M.</given-names></name></person-group><article-title>Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans</article-title><source>MBio</source><volume>3</volume><issue>6</issue><year>2012</year><fpage>e00473</fpage><lpage>512</lpage><pub-id pub-id-type="pmid">23170002</pub-id></element-citation></ref><ref id="b0040"><label>8</label><element-citation publication-type="journal" id="h0040"><person-group person-group-type="author"><name><surname>Frey</surname><given-names>K.G.</given-names></name><name><surname>Redden</surname><given-names>C.L.</given-names></name><name><surname>Bishop-Lilly</surname><given-names>K.A.</given-names></name><name><surname>Johnson</surname><given-names>R.</given-names></name><name><surname>Hensley</surname><given-names>L.E.</given-names></name><name><surname>Raviprakash</surname><given-names>K.</given-names></name></person-group><article-title>Full-genome sequence of human betacoronavirus 2c Jordan-N3/2012 after serial passage in mammalian cells</article-title><source>Genome Announc</source><volume>2</volume><issue>3</issue><year>2014</year><fpage>e00324</fpage><lpage>414</lpage><pub-id pub-id-type="pmid">24874668</pub-id></element-citation></ref><ref id="b0045"><label>9</label><element-citation publication-type="journal" id="h0045"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>J.F.</given-names></name><name><surname>Lau</surname><given-names>S.K.</given-names></name><name><surname>To</surname><given-names>K.K.</given-names></name><name><surname>Cheng</surname><given-names>V.C.</given-names></name><name><surname>Woo</surname><given-names>P.C.</given-names></name><name><surname>Yuen</surname><given-names>K.Y.</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease</article-title><source>Clin Microbiol Rev</source><volume>28</volume><issue>2</issue><year>2015</year><fpage>465</fpage><lpage>522</lpage><pub-id pub-id-type="pmid">25810418</pub-id></element-citation></ref><ref id="b0050"><label>10</label><element-citation publication-type="journal" id="h0050"><person-group person-group-type="author"><name><surname>Cotten</surname><given-names>M.</given-names></name><name><surname>Lam</surname><given-names>T.T.</given-names></name><name><surname>Watson</surname><given-names>S.J.</given-names></name><name><surname>Palser</surname><given-names>A.L.</given-names></name><name><surname>Petrova</surname><given-names>V.</given-names></name><name><surname>Grant</surname><given-names>P.</given-names></name></person-group><article-title>Full-genome deep sequencing and phylogenetic analysis of novel human betacoronavirus</article-title><source>Emerg Infect Dis</source><volume>19</volume><issue>5</issue><year>2013</year><fpage>736</fpage><lpage>742</lpage><pub-id pub-id-type="pmid">23693015</pub-id></element-citation></ref><ref id="b0055"><label>11</label><element-citation publication-type="journal" id="h0055"><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><article-title>MERS-coronavirus: from discovery to intervention</article-title><source>One Health</source><volume>3</volume><year>2016</year><fpage>11</fpage><lpage>16</lpage><pub-id pub-id-type="pmid">28616497</pub-id></element-citation></ref><ref id="b0060"><label>12</label><element-citation publication-type="journal" id="h0060"><person-group person-group-type="author"><name><surname>Li</surname><given-names>F.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Farzan</surname><given-names>M.</given-names></name><name><surname>Harrison</surname><given-names>S.C.</given-names></name></person-group><article-title>Structure of SARS coronavirus spike receptor-binding domain complexed with receptor</article-title><source>Science</source><volume>309</volume><issue>5742</issue><year>2005</year><fpage>1864</fpage><lpage>1868</lpage><pub-id pub-id-type="pmid">16166518</pub-id></element-citation></ref><ref id="b0065"><label>13</label><element-citation publication-type="journal" id="h0065"><person-group person-group-type="author"><name><surname>Du</surname><given-names>L.</given-names></name><name><surname>Kou</surname><given-names>Z.</given-names></name><name><surname>Ma</surname><given-names>C.</given-names></name><name><surname>Tao</surname><given-names>X.</given-names></name><name><surname>Wang</surname><given-names>L.</given-names></name><name><surname>Zhao</surname><given-names>G.</given-names></name></person-group><article-title>A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines</article-title><source>PLoS One</source><volume>8</volume><issue>12</issue><year>2013</year><object-id pub-id-type="publisher-id">e81587</object-id></element-citation></ref><ref id="b0070"><label>14</label><element-citation publication-type="journal" id="h0070"><person-group person-group-type="author"><name><surname>Lu</surname><given-names>G.</given-names></name><name><surname>Hu</surname><given-names>Y.</given-names></name><name><surname>Wang</surname><given-names>Q.</given-names></name><name><surname>Qi</surname><given-names>J.</given-names></name><name><surname>Gao</surname><given-names>F.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name></person-group><article-title>Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26</article-title><source>Nature</source><volume>500</volume><issue>7461</issue><year>2013</year><fpage>227</fpage><lpage>231</lpage><pub-id pub-id-type="pmid">23831647</pub-id></element-citation></ref><ref id="b0075"><label>15</label><element-citation publication-type="journal" id="h0075"><person-group person-group-type="author"><name><surname>Ma</surname><given-names>C.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Wang</surname><given-names>L.</given-names></name><name><surname>Zhao</surname><given-names>G.</given-names></name><name><surname>Tao</surname><given-names>X.</given-names></name><name><surname>Tseng</surname><given-names>C.T.</given-names></name></person-group><article-title>Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: implication for designing novel mucosal MERS vaccines</article-title><source>Vaccine</source><volume>32</volume><issue>18</issue><year>2014</year><fpage>2100</fpage><lpage>2108</lpage><pub-id pub-id-type="pmid">24560617</pub-id></element-citation></ref><ref id="b0080"><label>16</label><element-citation publication-type="journal" id="h0080"><person-group person-group-type="author"><name><surname>Mou</surname><given-names>H.</given-names></name><name><surname>Raj</surname><given-names>V.S.</given-names></name><name><surname>Van Kuppeveld</surname><given-names>F.J.</given-names></name><name><surname>Rottier</surname><given-names>P.J.</given-names></name><name><surname>Haagmans</surname><given-names>B.L.</given-names></name><name><surname>Bosch</surname><given-names>B.J.</given-names></name></person-group><article-title>The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies</article-title><source>J Virol</source><volume>87</volume><issue>16</issue><year>2013</year><fpage>9379</fpage><lpage>9383</lpage><pub-id pub-id-type="pmid">23785207</pub-id></element-citation></ref><ref id="b0085"><label>17</label><element-citation publication-type="journal" id="h0085"><person-group person-group-type="author"><name><surname>Lan</surname><given-names>J.</given-names></name><name><surname>Yao</surname><given-names>Y.</given-names></name><name><surname>Deng</surname><given-names>Y.</given-names></name><name><surname>Hu</surname><given-names>Y.</given-names></name><name><surname>Bao</surname><given-names>L.</given-names></name><name><surname>Huang</surname><given-names>B.</given-names></name></person-group><article-title>The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection</article-title><source>Vaccine</source><volume>35</volume><issue>1</issue><year>2017</year><fpage>10</fpage><lpage>18</lpage><pub-id pub-id-type="pmid">27899228</pub-id></element-citation></ref><ref id="b0090"><label>18</label><element-citation publication-type="journal" id="h0090"><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><article-title>Middle East respiratory syndrome</article-title><source>Lancet</source><volume>386</volume><issue>9997</issue><year>2015</year><fpage>995</fpage><lpage>1007</lpage><pub-id pub-id-type="pmid">26049252</pub-id></element-citation></ref><ref id="b0095"><label>19</label><element-citation publication-type="journal" id="h0095"><person-group person-group-type="author"><name><surname>Lu</surname><given-names>L.</given-names></name><name><surname>Liu</surname><given-names>Q.</given-names></name><name><surname>Zhu</surname><given-names>Y.</given-names></name><name><surname>Chan</surname><given-names>K.H.</given-names></name><name><surname>Qin</surname><given-names>L.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name></person-group><article-title>Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor</article-title><source>Nat Commun</source><volume>5</volume><year>2014</year><fpage>3067</fpage><pub-id pub-id-type="pmid">24473083</pub-id></element-citation></ref><ref id="b0100"><label>20</label><element-citation publication-type="journal" id="h0100"><person-group person-group-type="author"><name><surname>Millet</surname><given-names>J.K.</given-names></name><name><surname>Whittaker</surname><given-names>G.R.</given-names></name></person-group><article-title>Host cell proteases: critical determinants of coronavirus tropism and pathogenesis</article-title><source>Virus Res</source><volume>202</volume><year>2015</year><fpage>120</fpage><lpage>134</lpage><pub-id pub-id-type="pmid">25445340</pub-id></element-citation></ref><ref id="b0105"><label>21</label><element-citation publication-type="journal" id="h0105"><person-group person-group-type="author"><name><surname>Lu</surname><given-names>G.</given-names></name><name><surname>Wang</surname><given-names>Q.</given-names></name><name><surname>Gao</surname><given-names>G.F.</given-names></name></person-group><article-title>Bat-to-human: spike features determining “host jump” of coronaviruses SARS-CoV, MERS-CoV, and beyond</article-title><source>Trends Microbiol</source><volume>23</volume><issue>8</issue><year>2015</year><fpage>468</fpage><lpage>478</lpage><pub-id pub-id-type="pmid">26206723</pub-id></element-citation></ref><ref id="b0110"><label>22</label><element-citation publication-type="journal" id="h0110"><person-group person-group-type="author"><name><surname>Surya</surname><given-names>W.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Verdià-Bàguena</surname><given-names>C.</given-names></name><name><surname>Aguilella</surname><given-names>V.M.</given-names></name><name><surname>Torres</surname><given-names>J.</given-names></name></person-group><article-title>MERS coronavirus envelope protein has a single transmembrane domain that forms pentameric ion channels</article-title><source>Virus Res</source><volume>201</volume><year>2015</year><fpage>61</fpage><lpage>66</lpage><pub-id pub-id-type="pmid">25733052</pub-id></element-citation></ref><ref id="b0115"><label>23</label><element-citation publication-type="journal" id="h0115"><person-group person-group-type="author"><name><surname>Westerbeck</surname><given-names>J.W.</given-names></name><name><surname>Machamer</surname><given-names>C.E.</given-names></name></person-group><article-title>A coronavirus E protein is present in two distinct pools with different effects on assembly and the secretory pathway</article-title><source>J Virol</source><volume>89</volume><issue>18</issue><year>2015</year><fpage>9313</fpage><lpage>9323</lpage><pub-id pub-id-type="pmid">26136577</pub-id></element-citation></ref><ref id="b0120"><label>24</label><element-citation publication-type="journal" id="h0120"><person-group person-group-type="author"><name><surname>Xie</surname><given-names>Q.</given-names></name><name><surname>He</surname><given-names>X.</given-names></name><name><surname>Yang</surname><given-names>F.</given-names></name><name><surname>Liu</surname><given-names>X.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name></person-group><article-title>Analysis of the genome sequence and prediction of B-cell epitopes of the envelope protein of Middle East respiratory syndrome-coronavirus</article-title><source>IEEE/ACM Trans Comput Biol Bioinform</source><volume>15</volume><issue>4</issue><year>2018</year><fpage>1344</fpage><lpage>1350</lpage><pub-id pub-id-type="pmid">28574363</pub-id></element-citation></ref><ref id="b0125"><label>25</label><element-citation publication-type="journal" id="h0125"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>J.</given-names></name><name><surname>Sun</surname><given-names>Y.</given-names></name><name><surname>Qi</surname><given-names>J.</given-names></name><name><surname>Chu</surname><given-names>F.</given-names></name><name><surname>Wu</surname><given-names>H.</given-names></name><name><surname>Gao</surname><given-names>F.</given-names></name></person-group><article-title>The membrane protein of severe acute respiratory syndrome coronavirus acts as a dominant immunogen revealed by a clustering region of novel functionally and structurally defined cytotoxic T-lymphocyte epitopes</article-title><source>J Infect Dis</source><volume>202</volume><issue>8</issue><year>2010</year><fpage>1171</fpage><lpage>1180</lpage><pub-id pub-id-type="pmid">20831383</pub-id></element-citation></ref><ref id="b0130"><label>26</label><element-citation publication-type="journal" id="h0130"><person-group person-group-type="author"><name><surname>De Haan</surname><given-names>C.A.</given-names></name><name><surname>Rottier</surname><given-names>P.J.</given-names></name></person-group><article-title>Molecular interactions in the assembly of coronaviruses</article-title><source>Adv Virus Res</source><volume>64</volume><year>2005</year><fpage>165</fpage><lpage>230</lpage><pub-id pub-id-type="pmid">16139595</pub-id></element-citation></ref><ref id="b0135"><label>27</label><element-citation publication-type="journal" id="h0135"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>S.C.</given-names></name><name><surname>Ho</surname><given-names>C.T.</given-names></name><name><surname>Chuo</surname><given-names>W.H.</given-names></name><name><surname>Li</surname><given-names>S.</given-names></name><name><surname>Wang</surname><given-names>T.T.</given-names></name><name><surname>Lin</surname><given-names>C.C.</given-names></name></person-group><article-title>Effective inhibition of MERS-CoV infection by resveratrol</article-title><source>BMC Infect Dis</source><volume>17</volume><issue>1</issue><year>2017</year><fpage>144</fpage><pub-id pub-id-type="pmid">28193191</pub-id></element-citation></ref><ref id="b0140"><label>28</label><element-citation publication-type="journal" id="h0140"><person-group person-group-type="author"><name><surname>Szelazek</surname><given-names>B.</given-names></name><name><surname>Kabala</surname><given-names>W.</given-names></name><name><surname>Kus</surname><given-names>K.</given-names></name><name><surname>Zdzalik</surname><given-names>M.</given-names></name><name><surname>Twarda-Clapa</surname><given-names>A.</given-names></name><name><surname>Golik</surname><given-names>P.</given-names></name></person-group><article-title>Structural characterization of human coronavirus NL63 N protein</article-title><source>J Virol</source><volume>91</volume><issue>11</issue><year>2017</year><fpage>e02503</fpage><lpage>16</lpage><pub-id pub-id-type="pmid">28331093</pub-id></element-citation></ref><ref id="b0145"><label>29</label><element-citation publication-type="journal" id="h0145"><person-group person-group-type="author"><name><surname>Hu</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Gao</surname><given-names>T.</given-names></name><name><surname>Cui</surname><given-names>Y.</given-names></name><name><surname>Jin</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>P.</given-names></name></person-group><article-title>The severe acute respiratory syndrome coronavirus nucleocapsid inhibits type I interferon production by interfering with TRIM25-mediated RIG-I ubiquitination</article-title><source>J Virol</source><volume>91</volume><issue>8</issue><year>2017</year><fpage>e02143</fpage><lpage>16</lpage><pub-id pub-id-type="pmid">28148787</pub-id></element-citation></ref><ref id="b0150"><label>30</label><element-citation publication-type="journal" id="h0150"><person-group person-group-type="author"><name><surname>Grunewald</surname><given-names>M.E.</given-names></name><name><surname>Fehr</surname><given-names>A.R.</given-names></name><name><surname>Athmer</surname><given-names>J.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name></person-group><article-title>The coronavirus nucleocapsid protein is ADP-ribosylated</article-title><source>Virology</source><volume>517</volume><year>2018</year><fpage>62</fpage><lpage>68</lpage><pub-id pub-id-type="pmid">29199039</pub-id></element-citation></ref><ref id="b0155"><label>31</label><element-citation publication-type="journal" id="h0155"><person-group person-group-type="author"><name><surname>Papageorgiou</surname><given-names>N.</given-names></name><name><surname>Lichière</surname><given-names>J.</given-names></name><name><surname>Baklouti</surname><given-names>A.</given-names></name><name><surname>Ferron</surname><given-names>F.</given-names></name><name><surname>Sévajol</surname><given-names>M.</given-names></name><name><surname>Canard</surname><given-names>B.</given-names></name></person-group><article-title>Structural characterization of the N-terminal part of the MERS-CoV nucleocapsid by X-ray diffraction and small-angle X-ray scattering</article-title><source>Acta Crystallogr D Struct Biol</source><volume>72</volume><issue>Pt 2</issue><year>2016</year><fpage>192</fpage><lpage>202</lpage><pub-id pub-id-type="pmid">26894667</pub-id></element-citation></ref><ref id="b0160"><label>32</label><element-citation publication-type="journal" id="h0160"><person-group person-group-type="author"><name><surname>Banda</surname><given-names>N.K.</given-names></name><name><surname>Acharya</surname><given-names>S.</given-names></name><name><surname>Scheinman</surname><given-names>R.I.</given-names></name><name><surname>Mehta</surname><given-names>G.</given-names></name><name><surname>Takahashi</surname><given-names>M.</given-names></name><name><surname>Endo</surname><given-names>Y.</given-names></name></person-group><article-title>Deconstructing the lectin pathway in the pathogenesis of experimental inflammatory arthritis: essential role of the lectin ficolin B and mannose-binding protein-associated serine protease 2</article-title><source>J Immunol</source><volume>199</volume><issue>5</issue><year>2017</year><fpage>1835</fpage><lpage>1845</lpage><pub-id pub-id-type="pmid">28739878</pub-id></element-citation></ref><ref id="b0165"><label>33</label><element-citation publication-type="journal" id="h0165"><person-group person-group-type="author"><name><surname>Bolwig</surname><given-names>G.M.</given-names></name><name><surname>Bruder</surname><given-names>J.T.</given-names></name><name><surname>Hearing</surname><given-names>P.</given-names></name></person-group><article-title>Different binding site requirements for binding and activation for the bipartite enhancer factor EF-1A</article-title><source>Nucleic Acids Res</source><volume>20</volume><issue>24</issue><year>1992</year><fpage>6555</fpage><lpage>6564</lpage><pub-id pub-id-type="pmid">1336180</pub-id></element-citation></ref><ref id="b0170"><label>34</label><element-citation publication-type="journal" id="h0170"><person-group person-group-type="author"><name><surname>Forni</surname><given-names>D.</given-names></name><name><surname>Cagliani</surname><given-names>R.</given-names></name><name><surname>Clerici</surname><given-names>M.</given-names></name><name><surname>Sironi</surname><given-names>M.</given-names></name></person-group><article-title>Molecular evolution of human coronavirus genomes</article-title><source>Trends Microbiol</source><volume>25</volume><issue>1</issue><year>2017</year><fpage>35</fpage><lpage>48</lpage><pub-id pub-id-type="pmid">27743750</pub-id></element-citation></ref><ref id="b0175"><label>35</label><element-citation publication-type="journal" id="h0175"><person-group person-group-type="author"><name><surname>Menachery</surname><given-names>V.D.</given-names></name><name><surname>Mitchell</surname><given-names>H.D.</given-names></name><name><surname>Cockrell</surname><given-names>A.S.</given-names></name><name><surname>Gralinski</surname><given-names>L.E.</given-names></name><name><surname>Yount</surname><given-names>B.L.</given-names><suffix>Jr</suffix></name><name><surname>Graham</surname><given-names>R.L.</given-names></name></person-group><article-title>MERS-CoV accessory ORFs play key role for infection and pathogenesis</article-title><source>MBio</source><volume>8</volume><issue>4</issue><year>2017</year><fpage>e00665</fpage><lpage>717</lpage><pub-id pub-id-type="pmid">28830941</pub-id></element-citation></ref><ref id="b0180"><label>36</label><element-citation publication-type="journal" id="h0180"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>Y.</given-names></name><name><surname>Zhang</surname><given-names>L.</given-names></name><name><surname>Geng</surname><given-names>H.</given-names></name><name><surname>Deng</surname><given-names>Y.</given-names></name><name><surname>Huang</surname><given-names>B.</given-names></name><name><surname>Guo</surname><given-names>Y.</given-names></name></person-group><article-title>The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists</article-title><source>Protein Cell</source><volume>4</volume><issue>12</issue><year>2013</year><fpage>951</fpage><lpage>961</lpage><pub-id pub-id-type="pmid">24318862</pub-id></element-citation></ref><ref id="b0185"><label>37</label><element-citation publication-type="journal" id="h0185"><person-group person-group-type="author"><name><surname>Thornbrough</surname><given-names>J.M.</given-names></name><name><surname>Jha</surname><given-names>B.K.</given-names></name><name><surname>Yount</surname><given-names>B.</given-names></name><name><surname>Goldstein</surname><given-names>S.A.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Elliott</surname><given-names>R.</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus NS4b protein inhibits host RNase L activation</article-title><source>MBio</source><volume>7</volume><issue>2</issue><year>2016</year><object-id pub-id-type="publisher-id">e00258</object-id></element-citation></ref><ref id="b0190"><label>38</label><element-citation publication-type="journal" id="h0190"><person-group person-group-type="author"><name><surname>Rabouw</surname><given-names>H.H.</given-names></name><name><surname>Langereis</surname><given-names>M.A.</given-names></name><name><surname>Knaap</surname><given-names>R.C.</given-names></name><name><surname>Dalebout</surname><given-names>T.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><article-title>Middle East respiratory coronavirus accessory protein 4a inhibits PKR-mediated antiviral stress responses</article-title><source>PLoS Pathog</source><volume>12</volume><issue>10</issue><year>2016</year><object-id pub-id-type="publisher-id">e1005982</object-id></element-citation></ref><ref id="b0195"><label>39</label><element-citation publication-type="journal" id="h0195"><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><article-title>Coronaviruses—drug discovery and therapeutic options</article-title><source>Nat Rev Drug Discov</source><volume>15</volume><issue>5</issue><year>2016</year><fpage>327</fpage><lpage>347</lpage><pub-id pub-id-type="pmid">26868298</pub-id></element-citation></ref><ref id="b0200"><label>40</label><element-citation publication-type="journal" id="h0200"><person-group person-group-type="author"><name><surname>Lei</surname><given-names>J.</given-names></name><name><surname>Kusov</surname><given-names>Y.</given-names></name><name><surname>Hilgenfeld</surname><given-names>R.</given-names></name></person-group><article-title>Nsp3 of coronaviruses: structures and functions of a large multi-domain protein</article-title><source>Antiviral Res</source><volume>149</volume><year>2018</year><fpage>58</fpage><lpage>74</lpage><pub-id pub-id-type="pmid">29128390</pub-id></element-citation></ref><ref id="b0205"><label>41</label><element-citation publication-type="journal" id="h0205"><person-group person-group-type="author"><name><surname>Báez-Santos</surname><given-names>Y.M.</given-names></name><name><surname>St John</surname><given-names>S.E.</given-names></name><name><surname>Mesecar</surname><given-names>A.D.</given-names></name></person-group><article-title>The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds</article-title><source>Antiviral Res</source><volume>115</volume><year>2015</year><fpage>21</fpage><lpage>38</lpage><pub-id pub-id-type="pmid">25554382</pub-id></element-citation></ref><ref id="b0210"><label>42</label><element-citation publication-type="journal" id="h0210"><person-group person-group-type="author"><name><surname>Kankanamalage</surname><given-names>A.C.G.</given-names></name><name><surname>Kim</surname><given-names>Y.</given-names></name><name><surname>Damalanka</surname><given-names>V.C.</given-names></name><name><surname>Rathnayake</surname><given-names>A.D.</given-names></name><name><surname>Fehr</surname><given-names>A.R.</given-names></name><name><surname>Mehzabeen</surname><given-names>N.</given-names></name></person-group><article-title>Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element</article-title><source>Eur J Med Chem</source><volume>150</volume><year>2018</year><fpage>334</fpage><lpage>346</lpage><pub-id pub-id-type="pmid">29544147</pub-id></element-citation></ref><ref id="b0215"><label>43</label><element-citation publication-type="journal" id="h0215"><person-group person-group-type="author"><name><surname>Kandeel</surname><given-names>M.</given-names></name><name><surname>Altaher</surname><given-names>A.</given-names></name></person-group><article-title>Synonymous and biased codon usage by MERS CoV papain-like and 3CL-proteases</article-title><source>Biol Pharm Bull</source><volume>40</volume><issue>7</issue><year>2017</year><fpage>1086</fpage><lpage>1091</lpage><pub-id pub-id-type="pmid">28420819</pub-id></element-citation></ref><ref id="b0220"><label>44</label><element-citation publication-type="journal" id="h0220"><person-group person-group-type="author"><name><surname>Forni</surname><given-names>D.</given-names></name><name><surname>Cagliani</surname><given-names>R.</given-names></name><name><surname>Mozzi</surname><given-names>A.</given-names></name><name><surname>Pozzoli</surname><given-names>U.</given-names></name><name><surname>Al-Daghri</surname><given-names>N.</given-names></name><name><surname>Clerici</surname><given-names>M.</given-names></name></person-group><article-title>Extensive positive selection drives the evolution of nonstructural proteins in lineage C betacoronaviruses</article-title><source>J Virol</source><volume>90</volume><issue>7</issue><year>2016</year><fpage>3627</fpage><lpage>3639</lpage><pub-id pub-id-type="pmid">26792741</pub-id></element-citation></ref><ref id="b0225"><label>45</label><element-citation publication-type="journal" id="h0225"><person-group person-group-type="author"><name><surname>Oudshoorn</surname><given-names>D.</given-names></name><name><surname>Rijs</surname><given-names>K.</given-names></name><name><surname>Limpens</surname><given-names>R.W.A.L.</given-names></name><name><surname>Groen</surname><given-names>K.</given-names></name><name><surname>Koster</surname><given-names>A.J.</given-names></name><name><surname>Snijder</surname><given-names>E.J.</given-names></name></person-group><article-title>Expression and cleavage of Middle East respiratory syndrome coronavirus nsp3-4 polyprotein induce the formation of double-membrane vesicles that mimic those associated with coronaviral RNA replication</article-title><source>MBio</source><volume>8</volume><issue>6</issue><year>2017</year><fpage>e01658</fpage><lpage>717</lpage><pub-id pub-id-type="pmid">29162711</pub-id></element-citation></ref><ref id="b0230"><label>46</label><element-citation publication-type="journal" id="h0230"><person-group person-group-type="author"><name><surname>Terada</surname><given-names>Y.</given-names></name><name><surname>Kawachi</surname><given-names>K.</given-names></name><name><surname>Matsuura</surname><given-names>Y.</given-names></name><name><surname>Kamitani</surname><given-names>W.</given-names></name></person-group><article-title>MERS coronavirus nsp1 participates in an efficient propagation through a specific interaction with viral RNA</article-title><source>Virology</source><volume>511</volume><year>2017</year><fpage>95</fpage><lpage>105</lpage><pub-id pub-id-type="pmid">28843094</pub-id></element-citation></ref><ref id="b0235"><label>47</label><element-citation publication-type="journal" id="h0235"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>R.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Cowley</surname><given-names>T.J.</given-names></name><name><surname>Steinbrenner</surname><given-names>A.D.</given-names></name><name><surname>Phillips</surname><given-names>J.M.</given-names></name><name><surname>Yount</surname><given-names>B.L.</given-names></name></person-group><article-title>The nsp1, nsp13, and M proteins contribute to the hepatotropism of murine coronavirus JHM.WU</article-title><source>J Virol</source><volume>89</volume><issue>7</issue><year>2015</year><fpage>3598</fpage><lpage>3609</lpage><pub-id pub-id-type="pmid">25589656</pub-id></element-citation></ref><ref id="b0240"><label>48</label><element-citation publication-type="journal" id="h0240"><person-group person-group-type="author"><name><surname>Adedeji</surname><given-names>A.O.</given-names></name><name><surname>Lazarus</surname><given-names>H.</given-names></name></person-group><article-title>Biochemical characterization of Middle East respiratory syndrome coronavirus helicase</article-title><source>mSphere</source><volume>1</volume><issue>5</issue><year>2016</year><fpage>e00235</fpage><lpage>316</lpage><pub-id pub-id-type="pmid">27631026</pub-id></element-citation></ref><ref id="b0245"><label>49</label><element-citation publication-type="journal" id="h0245"><person-group person-group-type="author"><name><surname>Kindler</surname><given-names>E.</given-names></name><name><surname>Gil-Cruz</surname><given-names>C.</given-names></name><name><surname>Spanier</surname><given-names>J.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Wilhelm</surname><given-names>J.</given-names></name><name><surname>Rabouw</surname><given-names>H.H.</given-names></name></person-group><article-title>Early endonuclease-mediated evasion of RNA sensing ensures efficient coronavirus replication</article-title><source>PLoS Pathog</source><volume>13</volume><issue>2</issue><year>2017</year><object-id pub-id-type="publisher-id">e1006195</object-id></element-citation></ref><ref id="b0250"><label>50</label><element-citation publication-type="journal" id="h0250"><person-group person-group-type="author"><name><surname>Deng</surname><given-names>X.</given-names></name><name><surname>Hackbart</surname><given-names>M.</given-names></name><name><surname>Mettelman</surname><given-names>R.C.</given-names></name><name><surname>O’Brien</surname><given-names>A.</given-names></name><name><surname>Mielech</surname><given-names>A.M.</given-names></name><name><surname>Yi</surname><given-names>G.</given-names></name></person-group><article-title>Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages</article-title><source>Proc Natl Acad Sci USA</source><volume>114</volume><issue>21</issue><year>2017</year><fpage>E4251</fpage><lpage>E4260</lpage><pub-id pub-id-type="pmid">28484023</pub-id></element-citation></ref><ref id="b0255"><label>51</label><element-citation publication-type="journal" id="h0255"><person-group person-group-type="author"><name><surname>Aouadi</surname><given-names>W.</given-names></name><name><surname>Blanjoie</surname><given-names>A.</given-names></name><name><surname>Vasseur</surname><given-names>J.J.</given-names></name><name><surname>Debart</surname><given-names>F.</given-names></name><name><surname>Canard</surname><given-names>B.</given-names></name><name><surname>Decroly</surname><given-names>E.</given-names></name></person-group><article-title>Binding of the methyl donor <italic>S</italic>-adenosyl-<italic>I</italic>-methionine to Middle East respiratory syndrome coronavirus 2′-<italic>O</italic>-methyltransferase nsp16 promotes recruitment of the allosteric activator nsp10</article-title><source>J Virol</source><volume>91</volume><issue>5</issue><year>2017</year><fpage>e02217</fpage><lpage>316</lpage><pub-id pub-id-type="pmid">28031370</pub-id></element-citation></ref><ref id="b0260"><label>52</label><element-citation publication-type="journal" id="h0260"><person-group person-group-type="author"><name><surname>Angelini</surname><given-names>M.M.</given-names></name><name><surname>Akhlaghpour</surname><given-names>M.</given-names></name><name><surname>Neuman</surname><given-names>B.W.</given-names></name><name><surname>Buchmeier</surname><given-names>M.J.</given-names></name></person-group><article-title>Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4, and 6 induce double-membrane vesicles</article-title><source>MBio</source><volume>4</volume><issue>4</issue><year>2013</year><fpage>e00524</fpage><lpage>613</lpage></element-citation></ref><ref id="b0265"><label>53</label><element-citation publication-type="journal" id="h0265"><person-group person-group-type="author"><name><surname>Menachery</surname><given-names>V.D.</given-names></name><name><surname>Gralinski</surname><given-names>L.E.</given-names></name><name><surname>Mitchell</surname><given-names>H.D.</given-names></name><name><surname>Dinnon</surname><given-names>K.H.</given-names><suffix>3rd</suffix></name><name><surname>Leist</surname><given-names>S.R.</given-names></name><name><surname>Yount</surname><given-names>B.L.</given-names><suffix>Jr</suffix></name></person-group><article-title>Middle East respiratory syndrome coronavirus nonstructural protein 16 is necessary for interferon resistance and viral pathogenesis</article-title><source>mSphere</source><volume>2</volume><issue>6</issue><year>2017</year><fpage>e00346</fpage><lpage>417</lpage><pub-id pub-id-type="pmid">29152578</pub-id></element-citation></ref><ref id="b0270"><label>54</label><element-citation publication-type="journal" id="h0270"><person-group person-group-type="author"><name><surname>Alfuwaires</surname><given-names>M.</given-names></name><name><surname>Altaher</surname><given-names>A.</given-names></name><name><surname>Kandeel</surname><given-names>M.</given-names></name></person-group><article-title>Molecular dynamic studies of interferon and innate immunity resistance in MERS CoV Non-Structural Protein 3</article-title><source>Biol Pharm Bull</source><volume>40</volume><issue>3</issue><year>2017</year><fpage>345</fpage><lpage>351</lpage><pub-id pub-id-type="pmid">28250277</pub-id></element-citation></ref><ref id="b0275"><label>55</label><element-citation publication-type="journal" id="h0275"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>Y.P.</given-names></name><name><surname>Cho</surname><given-names>C.C.</given-names></name><name><surname>Chang</surname><given-names>C.F.</given-names></name><name><surname>Hsu</surname><given-names>C.H.</given-names></name></person-group><article-title>NMR assignments of the macro domain from Middle East respiratory syndrome coronavirus (MERS-CoV)</article-title><source>Biomol NMR Assign</source><volume>10</volume><issue>2</issue><year>2016</year><fpage>245</fpage><lpage>248</lpage><pub-id pub-id-type="pmid">26993639</pub-id></element-citation></ref><ref id="b0280"><label>56</label><element-citation publication-type="journal" id="h0280"><person-group person-group-type="author"><name><surname>Phua</surname><given-names>K.K.L.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Sim</surname><given-names>S.H.</given-names></name></person-group><article-title>Non-linear enhancement of mRNA delivery efficiencies by influenza A derived NS1 protein engendering host gene inhibition property</article-title><source>Biomaterials</source><volume>133</volume><year>2017</year><fpage>29</fpage><lpage>36</lpage><pub-id pub-id-type="pmid">28426973</pub-id></element-citation></ref><ref id="b0285"><label>57</label><element-citation publication-type="journal" id="h0285"><person-group person-group-type="author"><name><surname>Qian</surname><given-names>W.</given-names></name><name><surname>Wei</surname><given-names>X.</given-names></name><name><surname>Guo</surname><given-names>K.</given-names></name><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Lin</surname><given-names>X.</given-names></name><name><surname>Zou</surname><given-names>Z.</given-names></name></person-group><article-title>The C-terminal effector domain of non-structural protein 1 of influenza A virus blocks IFN-β production by targeting TNF receptor-associated factor 3</article-title><source>Front Immunol</source><volume>8</volume><year>2017</year><fpage>779</fpage><pub-id pub-id-type="pmid">28717359</pub-id></element-citation></ref><ref id="b0290"><label>58</label><element-citation publication-type="journal" id="h0290"><person-group person-group-type="author"><name><surname>Kuo</surname><given-names>R.L.</given-names></name><name><surname>Li</surname><given-names>L.H.</given-names></name><name><surname>Lin</surname><given-names>S.J.</given-names></name><name><surname>Li</surname><given-names>Z.H.</given-names></name><name><surname>Chen</surname><given-names>G.W.</given-names></name><name><surname>Chang</surname><given-names>C.K.</given-names></name></person-group><article-title>Role of N terminus-truncated NS1 proteins of influenza A virus in inhibiting IRF3 activation</article-title><source>J Virol</source><volume>90</volume><issue>9</issue><year>2016</year><fpage>4696</fpage><lpage>4705</lpage><pub-id pub-id-type="pmid">26912617</pub-id></element-citation></ref><ref id="b0295"><label>59</label><element-citation publication-type="journal" id="h0295"><person-group person-group-type="author"><name><surname>Schierhorn</surname><given-names>K.L.</given-names></name><name><surname>Jolmes</surname><given-names>F.</given-names></name><name><surname>Bespalowa</surname><given-names>J.</given-names></name><name><surname>Saenger</surname><given-names>S.</given-names></name><name><surname>Peteranderl</surname><given-names>C.</given-names></name><name><surname>Dzieciolowski</surname><given-names>J.</given-names></name></person-group><article-title>Influenza a virus virulence depends on two amino acids in the N-terminal domain of its NS1 protein to facilitate inhibition of the RNA-dependent protein kinase PKR</article-title><source>J Virol</source><volume>91</volume><issue>10</issue><year>2017</year><fpage>e00198</fpage><lpage>217</lpage><pub-id pub-id-type="pmid">28250123</pub-id></element-citation></ref><ref id="b0300"><label>60</label><element-citation publication-type="journal" id="h0300"><person-group person-group-type="author"><name><surname>Lokugamage</surname><given-names>K.G.</given-names></name><name><surname>Narayanan</surname><given-names>K.</given-names></name><name><surname>Nakagawa</surname><given-names>K.</given-names></name><name><surname>Terasaki</surname><given-names>K.</given-names></name><name><surname>Ramirez</surname><given-names>S.I.</given-names></name><name><surname>Tseng</surname><given-names>C.T.</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus nsp1 inhibits host gene expression by selectively targeting mRNAs transcribed in the nucleus while sparing mRNAs of cytoplasmic origin</article-title><source>J Virol</source><volume>89</volume><issue>21</issue><year>2015</year><fpage>10970</fpage><lpage>10981</lpage><pub-id pub-id-type="pmid">26311885</pub-id></element-citation></ref><ref id="b0305"><label>61</label><element-citation publication-type="journal" id="h0305"><person-group person-group-type="author"><name><surname>Peters</surname><given-names>H.L.</given-names></name><name><surname>Jochmans</surname><given-names>D.</given-names></name><name><surname>de Wilde</surname><given-names>A.H.</given-names></name><name><surname>Posthuma</surname><given-names>C.C.</given-names></name><name><surname>Snijder</surname><given-names>E.J.</given-names></name><name><surname>Neyts</surname><given-names>J.</given-names></name></person-group><article-title>Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity</article-title><source>Bioorg Med Chem Lett</source><volume>25</volume><issue>15</issue><year>2015</year><fpage>2923</fpage><lpage>2926</lpage><pub-id pub-id-type="pmid">26048809</pub-id></element-citation></ref><ref id="b0310"><label>62</label><element-citation publication-type="journal" id="h0310"><person-group person-group-type="author"><name><surname>Dyall</surname><given-names>J.</given-names></name><name><surname>Coleman</surname><given-names>C.M.</given-names></name><name><surname>Hart</surname><given-names>B.J.</given-names></name><name><surname>Venkataraman</surname><given-names>T.</given-names></name><name><surname>Holbrook</surname><given-names>M.R.</given-names></name><name><surname>Kindrachuk</surname><given-names>J.</given-names></name></person-group><article-title>Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection</article-title><source>Antimicrob Agents Chemother</source><volume>58</volume><issue>8</issue><year>2014</year><fpage>4885</fpage><lpage>4893</lpage><pub-id pub-id-type="pmid">24841273</pub-id></element-citation></ref><ref id="b0315"><label>63</label><element-citation publication-type="journal" id="h0315"><person-group person-group-type="author"><name><surname>De Wilde</surname><given-names>A.H.</given-names></name><name><surname>Raj</surname><given-names>V.S.</given-names></name><name><surname>Oudshoorn</surname><given-names>D.</given-names></name><name><surname>Bestebroer</surname><given-names>T.M.</given-names></name><name><surname>Van Nieuwkoop</surname><given-names>S.</given-names></name><name><surname>Limpens</surname><given-names>R.W.</given-names></name></person-group><article-title>MERS-coronavirus replication induces severe <italic>in vitro</italic> cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment</article-title><source>J Gen Virol</source><volume>94</volume><issue>Pt 8</issue><year>2013</year><fpage>1749</fpage><lpage>1760</lpage><pub-id pub-id-type="pmid">23620378</pub-id></element-citation></ref><ref id="b0320"><label>64</label><element-citation publication-type="journal" id="h0320"><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><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><issue>1</issue><year>2018</year><fpage>9</fpage><lpage>17</lpage><pub-id pub-id-type="pmid">28864360</pub-id></element-citation></ref><ref id="b0325"><label>65</label><element-citation publication-type="journal" id="h0325"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>Y.S.</given-names></name><name><surname>Son</surname><given-names>A.</given-names></name><name><surname>Kim</surname><given-names>J.</given-names></name><name><surname>Kwon</surname><given-names>S.B.</given-names></name><name><surname>Kim</surname><given-names>M.H.</given-names></name><name><surname>Kim</surname><given-names>P.</given-names></name></person-group><article-title>Chaperna-mediated assembly of ferritin-based Middle East respiratory syndrome-coronavirus nanoparticles</article-title><source>Front Immunol</source><volume>9</volume><year>2018</year><fpage>1093</fpage><pub-id pub-id-type="pmid">29868035</pub-id></element-citation></ref><ref id="b0330"><label>66</label><element-citation publication-type="journal" id="h0330"><person-group person-group-type="author"><name><surname>Corti</surname><given-names>D.</given-names></name><name><surname>Passini</surname><given-names>N.</given-names></name><name><surname>Lanzavecchia</surname><given-names>A.</given-names></name><name><surname>Zambon</surname><given-names>M.</given-names></name></person-group><article-title>Rapid generation of a human monoclonal antibody to combat Middle East respiratory syndrome</article-title><source>J Infect Public Health</source><volume>9</volume><issue>3</issue><year>2016</year><fpage>231</fpage><lpage>235</lpage><pub-id pub-id-type="pmid">27102927</pub-id></element-citation></ref><ref id="b0335"><label>67</label><element-citation publication-type="journal" id="h0335"><person-group person-group-type="author"><name><surname>Tang</surname><given-names>X.C.</given-names></name><name><surname>Agnihothram</surname><given-names>S.S.</given-names></name><name><surname>Jiao</surname><given-names>Y.</given-names></name><name><surname>Stanhope</surname><given-names>J.</given-names></name><name><surname>Graham</surname><given-names>R.L.</given-names></name><name><surname>Peterson</surname><given-names>E.C.</given-names></name></person-group><article-title>Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution</article-title><source>Proc Natl Acad Sci USA</source><volume>111</volume><issue>19</issue><year>2014</year><fpage>E2018</fpage><lpage>E2026</lpage><pub-id pub-id-type="pmid">24778221</pub-id></element-citation></ref><ref id="b0340"><label>68</label><element-citation publication-type="journal" id="h0340"><person-group person-group-type="author"><name><surname>Jiang</surname><given-names>L.</given-names></name><name><surname>Wang</surname><given-names>N.</given-names></name><name><surname>Zuo</surname><given-names>T.</given-names></name><name><surname>Shi</surname><given-names>X.</given-names></name><name><surname>Poon</surname><given-names>K.M.</given-names></name><name><surname>Wu</surname><given-names>Y.</given-names></name></person-group><article-title>Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein</article-title><source>Sci Transl Med</source><volume>6</volume><issue>234</issue><year>2014</year><fpage>234ra59</fpage></element-citation></ref><ref id="b0345"><label>69</label><element-citation publication-type="journal" id="h0345"><person-group person-group-type="author"><name><surname>Niu</surname><given-names>P.</given-names></name><name><surname>Zhang</surname><given-names>S.</given-names></name><name><surname>Zhou</surname><given-names>P.</given-names></name><name><surname>Huang</surname><given-names>B.</given-names></name><name><surname>Deng</surname><given-names>Y.</given-names></name><name><surname>Qin</surname><given-names>K.</given-names></name></person-group><article-title>Ultrapotent human neutralizing antibody repertoires against Middle East respiratory syndrome coronavirus from a recovered patient</article-title><source>J Infect Dis</source><volume>218</volume><issue>8</issue><year>2018</year><fpage>1249</fpage><lpage>1260</lpage><pub-id pub-id-type="pmid">29846635</pub-id></element-citation></ref><ref id="b0350"><label>70</label><element-citation publication-type="journal" id="h0350"><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></person-group><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><issue>28</issue><year>2015</year><fpage>8738</fpage><lpage>8743</lpage><pub-id pub-id-type="pmid">26124093</pub-id></element-citation></ref><ref id="b0355"><label>71</label><element-citation publication-type="journal" id="h0355"><person-group person-group-type="author"><name><surname>De Wit</surname><given-names>E.</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>Horne</surname><given-names>E.</given-names></name><name><surname>Haddock</surname><given-names>E.</given-names></name><name><surname>Saturday</surname><given-names>G.</given-names></name></person-group><article-title>Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets</article-title><source>Antiviral Res</source><volume>156</volume><year>2018</year><fpage>64</fpage><lpage>71</lpage><pub-id pub-id-type="pmid">29885377</pub-id></element-citation></ref><ref id="b0360"><label>72</label><element-citation publication-type="journal" id="h0360"><person-group person-group-type="author"><name><surname>Du</surname><given-names>L.</given-names></name><name><surname>Zhao</surname><given-names>G.</given-names></name><name><surname>Yang</surname><given-names>Y.</given-names></name><name><surname>Qiu</surname><given-names>H.</given-names></name><name><surname>Wang</surname><given-names>L.</given-names></name><name><surname>Kou</surname><given-names>Z.</given-names></name></person-group><article-title>A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein</article-title><source>J Virol</source><volume>88</volume><issue>12</issue><year>2014</year><fpage>7045</fpage><lpage>7053</lpage><pub-id pub-id-type="pmid">24719424</pub-id></element-citation></ref><ref id="b0365"><label>73</label><element-citation publication-type="journal" id="h0365"><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><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><issue>9</issue><year>2017</year><fpage>1261</fpage><lpage>1274</lpage><pub-id pub-id-type="pmid">28855003</pub-id></element-citation></ref><ref id="b0370"><label>74</label><element-citation publication-type="journal" id="h0370"><person-group person-group-type="author"><name><surname>Qiu</surname><given-names>H.</given-names></name><name><surname>Sun</surname><given-names>S.</given-names></name><name><surname>Xiao</surname><given-names>H.</given-names></name><name><surname>Feng</surname><given-names>J.</given-names></name><name><surname>Guo</surname><given-names>Y.</given-names></name><name><surname>Tai</surname><given-names>W.</given-names></name></person-group><article-title>Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection</article-title><source>Antiviral Res</source><volume>132</volume><year>2016</year><fpage>141</fpage><lpage>148</lpage><pub-id pub-id-type="pmid">27312105</pub-id></element-citation></ref><ref id="b0375"><label>75</label><element-citation publication-type="journal" id="h0375"><person-group person-group-type="author"><name><surname>Li</surname><given-names>Y.</given-names></name><name><surname>Wan</surname><given-names>Y.</given-names></name><name><surname>Liu</surname><given-names>P.</given-names></name><name><surname>Zhao</surname><given-names>J.</given-names></name><name><surname>Lu</surname><given-names>G.</given-names></name><name><surname>Qi</surname><given-names>J.</given-names></name></person-group><article-title>A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein</article-title><source>Cell Res</source><volume>25</volume><issue>11</issue><year>2015</year><fpage>1237</fpage><lpage>1249</lpage><pub-id pub-id-type="pmid">26391698</pub-id></element-citation></ref><ref id="b0380"><label>76</label><element-citation publication-type="journal" id="h0380"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>N.</given-names></name><name><surname>Channappanavar</surname><given-names>R.</given-names></name><name><surname>Ma</surname><given-names>C.</given-names></name><name><surname>Wang</surname><given-names>L.</given-names></name><name><surname>Tang</surname><given-names>J.</given-names></name><name><surname>Garron</surname><given-names>T.</given-names></name></person-group><article-title>Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus</article-title><source>Cell Mol Immunol</source><volume>13</volume><issue>2</issue><year>2016</year><fpage>180</fpage><lpage>190</lpage><pub-id pub-id-type="pmid">25640653</pub-id></element-citation></ref><ref id="b0385"><label>77</label><element-citation publication-type="journal" id="h0385"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>L.</given-names></name><name><surname>Shi</surname><given-names>W.</given-names></name><name><surname>Joyce</surname><given-names>M.G.</given-names></name><name><surname>Modjarrad</surname><given-names>K.</given-names></name><name><surname>Zhang</surname><given-names>Y.</given-names></name><name><surname>Leung</surname><given-names>K.</given-names></name></person-group><article-title>Evaluation of candidate vaccine approaches for MERS-CoV</article-title><source>Nat Commun</source><volume>6</volume><year>2015</year><fpage>7712</fpage><pub-id pub-id-type="pmid">26218507</pub-id></element-citation></ref><ref id="b0390"><label>78</label><element-citation publication-type="journal" id="h0390"><person-group person-group-type="author"><name><surname>Shirato</surname><given-names>K.</given-names></name><name><surname>Kawase</surname><given-names>M.</given-names></name><name><surname>Matsuyama</surname><given-names>S.</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2</article-title><source>J Virol</source><volume>87</volume><issue>23</issue><year>2013</year><fpage>12552</fpage><lpage>12561</lpage><pub-id pub-id-type="pmid">24027332</pub-id></element-citation></ref><ref id="b0395"><label>79</label><element-citation publication-type="journal" id="h0395"><person-group person-group-type="author"><name><surname>Gierer</surname><given-names>S.</given-names></name><name><surname>Bertram</surname><given-names>S.</given-names></name><name><surname>Kaup</surname><given-names>F.</given-names></name><name><surname>Wrensch</surname><given-names>F.</given-names></name><name><surname>Heurich</surname><given-names>A.</given-names></name><name><surname>Krämer-Kühl</surname><given-names>A.</given-names></name></person-group><article-title>The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies</article-title><source>J Virol</source><volume>87</volume><issue>10</issue><year>2013</year><fpage>5502</fpage><lpage>5511</lpage><pub-id pub-id-type="pmid">23468491</pub-id></element-citation></ref><ref id="b0400"><label>80</label><element-citation publication-type="journal" id="h0400"><person-group person-group-type="author"><name><surname>Millet</surname><given-names>J.K.</given-names></name><name><surname>Whittaker</surname><given-names>G.R.</given-names></name></person-group><article-title>Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein</article-title><source>Proc Natl Acad Sci USA</source><volume>111</volume><issue>42</issue><year>2014</year><fpage>15214</fpage><lpage>15219</lpage><pub-id pub-id-type="pmid">25288733</pub-id></element-citation></ref><ref id="b0405"><label>81</label><element-citation publication-type="journal" id="h0405"><person-group person-group-type="author"><name><surname>Coleman</surname><given-names>C.M.</given-names></name><name><surname>Sisk</surname><given-names>J.M.</given-names></name><name><surname>Mingo</surname><given-names>R.M.</given-names></name><name><surname>Nelson</surname><given-names>E.A.</given-names></name><name><surname>White</surname><given-names>J.M.</given-names></name><name><surname>Frieman</surname><given-names>M.B.</given-names></name></person-group><article-title>Abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus fusion</article-title><source>J Virol</source><volume>90</volume><issue>19</issue><year>2016</year><fpage>8924</fpage><lpage>8933</lpage><pub-id pub-id-type="pmid">27466418</pub-id></element-citation></ref><ref id="b0410"><label>82</label><element-citation publication-type="journal" id="h0410"><person-group person-group-type="author"><name><surname>Wrensch</surname><given-names>F.</given-names></name><name><surname>Winkler</surname><given-names>M.</given-names></name><name><surname>Pöhlmann</surname><given-names>S.</given-names></name></person-group><article-title>IFITM proteins inhibit entry driven by the MERS-coronavirus spike protein: evidence for cholesterol-independent mechanisms</article-title><source>Viruses</source><volume>6</volume><issue>9</issue><year>2014</year><fpage>3683</fpage><lpage>3698</lpage><pub-id pub-id-type="pmid">25256397</pub-id></element-citation></ref><ref id="b0415"><label>83</label><element-citation publication-type="journal" id="h0415"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>S.</given-names></name><name><surname>Wu</surname><given-names>S.</given-names></name><name><surname>Jiang</surname><given-names>S.</given-names></name></person-group><article-title>HIV entry inhibitors targeting gp41: from polypeptides to small-molecule compounds</article-title><source>Curr Pharm Des</source><volume>13</volume><issue>2</issue><year>2007</year><fpage>143</fpage><lpage>162</lpage><pub-id pub-id-type="pmid">17269924</pub-id></element-citation></ref><ref id="b0420"><label>84</label><element-citation publication-type="journal" id="h0420"><person-group person-group-type="author"><name><surname>Fehr</surname><given-names>A.R.</given-names></name><name><surname>Perlman</surname><given-names>S.</given-names></name></person-group><article-title>Coronaviruses: an overview of their replication and pathogenesis</article-title><source>Methods Mol Biol</source><volume>1282</volume><year>2015</year><fpage>1</fpage><lpage>23</lpage><pub-id pub-id-type="pmid">25720466</pub-id></element-citation></ref><ref id="b0425"><label>85</label><element-citation publication-type="journal" id="h0425"><person-group person-group-type="author"><name><surname>Kirchdoerfer</surname><given-names>R.N.</given-names></name><name><surname>Cottrell</surname><given-names>C.A.</given-names></name><name><surname>Wang</surname><given-names>N.</given-names></name><name><surname>Pallesen</surname><given-names>J.</given-names></name><name><surname>Yassine</surname><given-names>H.M.</given-names></name><name><surname>Turner</surname><given-names>H.L.</given-names></name></person-group><article-title>Pre-fusion structure of a human coronavirus spike protein</article-title><source>Nature</source><volume>531</volume><issue>7592</issue><year>2016</year><fpage>118</fpage><lpage>121</lpage><pub-id pub-id-type="pmid">26935699</pub-id></element-citation></ref><ref id="b0430"><label>86</label><element-citation publication-type="journal" id="h0430"><person-group person-group-type="author"><name><surname>Walls</surname><given-names>A.C.</given-names></name><name><surname>Tortorici</surname><given-names>M.A.</given-names></name><name><surname>Frenz</surname><given-names>B.</given-names></name><name><surname>Snijder</surname><given-names>J.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Rey</surname><given-names>F.A.</given-names></name></person-group><article-title>Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy</article-title><source>Nat Struct Mol Biol</source><volume>23</volume><issue>10</issue><year>2016</year><fpage>899</fpage><lpage>905</lpage><pub-id pub-id-type="pmid">27617430</pub-id></element-citation></ref><ref id="b0435"><label>87</label><element-citation publication-type="journal" id="h0435"><person-group person-group-type="author"><name><surname>Walls</surname><given-names>A.</given-names></name><name><surname>Tortorici</surname><given-names>M.A.</given-names></name><name><surname>Bosch</surname><given-names>B.J.</given-names></name><name><surname>Frenz</surname><given-names>B.</given-names></name><name><surname>Rottier</surname><given-names>P.J.</given-names></name><name><surname>DiMaio</surname><given-names>F.</given-names></name></person-group><article-title>Crucial steps in the structure determination of a coronavirus spike glycoprotein using cryo-electron microscopy</article-title><source>Protein Sci</source><volume>26</volume><issue>1</issue><year>2017</year><fpage>113</fpage><lpage>121</lpage><pub-id pub-id-type="pmid">27667334</pub-id></element-citation></ref><ref id="b0440"><label>88</label><element-citation publication-type="journal" id="h0440"><person-group person-group-type="author"><name><surname>Gao</surname><given-names>X.</given-names></name><name><surname>Zhou</surname><given-names>H.</given-names></name><name><surname>Wu</surname><given-names>C.</given-names></name><name><surname>Xiao</surname><given-names>Y.</given-names></name><name><surname>Ren</surname><given-names>L.</given-names></name><name><surname>Paranhos-Baccalà</surname><given-names>G.</given-names></name></person-group><article-title>Antibody against nucleocapsid protein predicts susceptibility to human coronavirus infection</article-title><source>J Infect</source><volume>71</volume><issue>5</issue><year>2015</year><fpage>599</fpage><lpage>602</lpage><pub-id pub-id-type="pmid">26165609</pub-id></element-citation></ref><ref id="b0445"><label>89</label><element-citation publication-type="journal" id="h0445"><person-group person-group-type="author"><name><surname>Yamaoka</surname><given-names>Y.</given-names></name><name><surname>Matsuyama</surname><given-names>S.</given-names></name><name><surname>Fukushi</surname><given-names>S.</given-names></name><name><surname>Matsunaga</surname><given-names>S.</given-names></name><name><surname>Matsushima</surname><given-names>Y.</given-names></name><name><surname>Kuroyama</surname><given-names>H.</given-names></name></person-group><article-title>Development of monoclonal antibody and diagnostic test for Middle East respiratory syndrome coronavirus using cell-free synthesized nucleocapsid antigen</article-title><source>Front Microbiol</source><volume>7</volume><year>2016</year><fpage>50</fpage><pub-id pub-id-type="pmid">26941711</pub-id></element-citation></ref></ref-list><ack id="ak005"><sec id="s0195"><title>Acknowledgements</title><p id="p0205">This work was supported by the <funding-source id="gp005">National Science and Technology</funding-source> Major Project for the Control and Prevention of Major Infectious Diseases in China (2018ZX10711001 and 2018ZX10102001).</p></sec><sec id="s0200"><title>Compliance with ethics guidelines</title><p id="p0210">Yan-Hua Li, Chen-Yu Hu, Nan-Ping Wu, Hang-Ping Yao, and Lan-Juan Li declare that they have no conflict of interest or financial conflicts to disclose.</p></sec></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001317 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001317 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:7104727
|texte= Molecular Characteristics, Functions, and Related Pathogenicity of MERS-CoV Proteins
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:32288963" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |