Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential
Identifieur interne : 000035 ( Pmc/Corpus ); précédent : 000034; suivant : 000036Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential
Auteurs : Jimin Xu ; Pei-Yong Shi ; Hongmin Li ; Jia ZhouSource :
- ACS Infectious Diseases [ 2373-8227 ] ; 2020.
Abstract
The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide, an FDA-approved anthelminthic drug, was found to be effective against various viral infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV, and human adenovirus, indicating its potential as an antiviral agent. In this brief review, we summarize the broad antiviral activity of niclosamide and highlight its potential clinical use in the treatment of COVID-19.
Url:
DOI: 10.1021/acsinfecdis.0c00052
PubMed: 32125140
PubMed Central: 7098069
Links to Exploration step
PMC:7098069Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic
Potential</title><author><name sortKey="Xu, Jimin" sort="Xu, Jimin" uniqKey="Xu J" first="Jimin" last="Xu">Jimin Xu</name><affiliation><nlm:aff id="aff1">Chemical Biology Program, Department of Pharmacology and Toxicology,</nlm:aff></affiliation></author><author><name sortKey="Shi, Pei Yong" sort="Shi, Pei Yong" uniqKey="Shi P" first="Pei-Yong" last="Shi">Pei-Yong Shi</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Department of Biochemistry and Molecular Biology</nlm:aff></affiliation><affiliation><nlm:aff id="aff1">Sealy Center for Structural Biology & Molecular Biophysics,<institution>University of Texas Medical Branch</institution>, Galveston, Texas 77555,<country>United States</country></nlm:aff></affiliation></author><author><name sortKey="Li, Hongmin" sort="Li, Hongmin" uniqKey="Li H" first="Hongmin" last="Li">Hongmin Li</name><affiliation><nlm:aff id="aff2"><institution>Wadsworth Center, New York State Department of Health</institution>, 120 New Scotland Avenue, Albany, New York 12208,<country>United States</country></nlm:aff></affiliation></author><author><name sortKey="Zhou, Jia" sort="Zhou, Jia" uniqKey="Zhou J" first="Jia" last="Zhou">Jia Zhou</name><affiliation><nlm:aff id="aff1">Chemical Biology Program, Department of Pharmacology and Toxicology,</nlm:aff></affiliation><affiliation><nlm:aff id="aff1">Sealy Center for Structural Biology & Molecular Biophysics,<institution>University of Texas Medical Branch</institution>, Galveston, Texas 77555,<country>United States</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32125140</idno><idno type="pmc">7098069</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098069</idno><idno type="RBID">PMC:7098069</idno><idno type="doi">10.1021/acsinfecdis.0c00052</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000035</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000035</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic
Potential</title><author><name sortKey="Xu, Jimin" sort="Xu, Jimin" uniqKey="Xu J" first="Jimin" last="Xu">Jimin Xu</name><affiliation><nlm:aff id="aff1">Chemical Biology Program, Department of Pharmacology and Toxicology,</nlm:aff></affiliation></author><author><name sortKey="Shi, Pei Yong" sort="Shi, Pei Yong" uniqKey="Shi P" first="Pei-Yong" last="Shi">Pei-Yong Shi</name><affiliation><nlm:aff wicri:cut=", and" id="aff1">Department of Biochemistry and Molecular Biology</nlm:aff></affiliation><affiliation><nlm:aff id="aff1">Sealy Center for Structural Biology & Molecular Biophysics,<institution>University of Texas Medical Branch</institution>, Galveston, Texas 77555,<country>United States</country></nlm:aff></affiliation></author><author><name sortKey="Li, Hongmin" sort="Li, Hongmin" uniqKey="Li H" first="Hongmin" last="Li">Hongmin Li</name><affiliation><nlm:aff id="aff2"><institution>Wadsworth Center, New York State Department of Health</institution>, 120 New Scotland Avenue, Albany, New York 12208,<country>United States</country></nlm:aff></affiliation></author><author><name sortKey="Zhou, Jia" sort="Zhou, Jia" uniqKey="Zhou J" first="Jia" last="Zhou">Jia Zhou</name><affiliation><nlm:aff id="aff1">Chemical Biology Program, Department of Pharmacology and Toxicology,</nlm:aff></affiliation><affiliation><nlm:aff id="aff1">Sealy Center for Structural Biology & Molecular Biophysics,<institution>University of Texas Medical Branch</institution>, Galveston, Texas 77555,<country>United States</country></nlm:aff></affiliation></author></analytic><series><title level="j">ACS Infectious Diseases</title><idno type="eISSN">2373-8227</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="id0c00052_0003" id="ab-tgr1"></graphic></p><p>The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need
for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide,
an FDA-approved anthelminthic drug, was found to be effective against various viral
infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV,
and human adenovirus, indicating its potential as an antiviral agent. In this brief
review, we summarize the broad antiviral activity of niclosamide and highlight its
potential clinical use in the treatment of COVID-19.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C. Huang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Ren, L" uniqKey="Ren L">L. Ren</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J. Zhao</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y. Hu</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Fan, G" uniqKey="Fan G">G. Fan</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J. Xu</name></author><author><name sortKey="Gu, X" uniqKey="Gu X">X. Gu</name></author><author><name sortKey="Cheng, Z" uniqKey="Cheng Z">Z. Cheng</name></author><author><name sortKey="Yu, T" uniqKey="Yu T">T. Yu</name></author><author><name sortKey="Xia, J" uniqKey="Xia J">J. Xia</name></author><author><name sortKey="Wei, Y" uniqKey="Wei Y">Y. Wei</name></author><author><name sortKey="Wu, W" uniqKey="Wu W">W. Wu</name></author><author><name sortKey="Xie, X" uniqKey="Xie X">X. Xie</name></author><author><name sortKey="Yin, W" uniqKey="Yin W">W. Yin</name></author><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author><author><name sortKey="Liu, M" uniqKey="Liu M">M. Liu</name></author><author><name sortKey="Xiao, Y" uniqKey="Xiao Y">Y. Xiao</name></author><author><name sortKey="Gao, H" uniqKey="Gao H">H. Gao</name></author><author><name sortKey="Guo, L" uniqKey="Guo L">L. Guo</name></author><author><name sortKey="Xie, J" uniqKey="Xie J">J. Xie</name></author><author><name sortKey="Wang, G" uniqKey="Wang G">G. Wang</name></author><author><name sortKey="Jiang, R" uniqKey="Jiang R">R. Jiang</name></author><author><name sortKey="Gao, Z" uniqKey="Gao Z">Z. Gao</name></author><author><name sortKey="Jin, Q" uniqKey="Jin Q">Q. Jin</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Cao, B" uniqKey="Cao B">B. Cao</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="Hui, D S" uniqKey="Hui D">D. S. Hui</name></author><author><name sortKey="I Azhar, E" uniqKey="I Azhar E">E. I Azhar</name></author><author><name sortKey="Madani, T A" uniqKey="Madani T">T. A. Madani</name></author><author><name sortKey="Ntoumi, F" uniqKey="Ntoumi F">F. Ntoumi</name></author><author><name sortKey="Kock, R" uniqKey="Kock R">R. Kock</name></author><author><name sortKey="Dar, O" uniqKey="Dar O">O. Dar</name></author><author><name sortKey="Ippolito, G" uniqKey="Ippolito G">G. Ippolito</name></author><author><name sortKey="Mchugh, T D" uniqKey="Mchugh T">T. D. McHugh</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z. A. Memish</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Petersen, E" uniqKey="Petersen E">E. Petersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, J F W" uniqKey="Chan J">J. F.-W. Chan</name></author><author><name sortKey="Yuan, S" uniqKey="Yuan S">S. Yuan</name></author><author><name sortKey="Kok, K H" uniqKey="Kok K">K.-H. Kok</name></author><author><name sortKey="To, K K W" uniqKey="To K">K. K.-W. To</name></author><author><name sortKey="Chu, H" uniqKey="Chu H">H. Chu</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J. Yang</name></author><author><name sortKey="Xing, F" uniqKey="Xing F">F. Xing</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="Yip, C C Y" uniqKey="Yip C">C. C.-Y. Yip</name></author><author><name sortKey="Poon, R W S" uniqKey="Poon R">R. W.-S. Poon</name></author><author><name sortKey="Tsoi, H W" uniqKey="Tsoi H">H.-W. Tsoi</name></author><author><name sortKey="Lo, S K F" uniqKey="Lo S">S. K.-F. Lo</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K.-H. Chan</name></author><author><name sortKey="Poon, V K M" uniqKey="Poon V">V. K.-M. Poon</name></author><author><name sortKey="Chan, W M" uniqKey="Chan W">W.-M. Chan</name></author><author><name sortKey="Ip, J D" uniqKey="Ip J">J. D. Ip</name></author><author><name sortKey="Cai, J P" uniqKey="Cai J">J.-P. Cai</name></author><author><name sortKey="Cheng, V C C" uniqKey="Cheng V">V. C.-C. Cheng</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Hui, C K M" uniqKey="Hui C">C. K.-M. Hui</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.-Y. Yuen</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Chan, J F W" uniqKey="Chan J">J. F. W. Chan</name></author><author><name sortKey="Azhar, E I" uniqKey="Azhar E">E. I. Azhar</name></author><author><name sortKey="Hui, D S C" uniqKey="Hui D">D. S. C. Hui</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.-Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holshue, M L" uniqKey="Holshue M">M. L. Holshue</name></author><author><name sortKey="Debolt, C" uniqKey="Debolt C">C. DeBolt</name></author><author><name sortKey="Lindquist, S" uniqKey="Lindquist S">S. Lindquist</name></author><author><name sortKey="Lofy, K H" uniqKey="Lofy K">K. H. Lofy</name></author><author><name sortKey="Wiesman, J" uniqKey="Wiesman J">J. Wiesman</name></author><author><name sortKey="Bruce, H" uniqKey="Bruce H">H. Bruce</name></author><author><name sortKey="Spitters, C" uniqKey="Spitters C">C. Spitters</name></author><author><name sortKey="Ericson, K" uniqKey="Ericson K">K. Ericson</name></author><author><name sortKey="Wilkerson, S" uniqKey="Wilkerson S">S. Wilkerson</name></author><author><name sortKey="Tural, A" uniqKey="Tural A">A. Tural</name></author><author><name sortKey="Diaz, G" uniqKey="Diaz G">G. Diaz</name></author><author><name sortKey="Cohn, A" uniqKey="Cohn A">A. Cohn</name></author><author><name sortKey="Fox, L" uniqKey="Fox L">L. Fox</name></author><author><name sortKey="Patel, A" uniqKey="Patel A">A. Patel</name></author><author><name sortKey="Gerber, S I" uniqKey="Gerber S">S. I. Gerber</name></author><author><name sortKey="Kim, L" uniqKey="Kim L">L. Kim</name></author><author><name sortKey="Tong, S" uniqKey="Tong S">S. Tong</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author><author><name sortKey="Lindstrom, S" uniqKey="Lindstrom S">S. Lindstrom</name></author><author><name sortKey="Pallansch, M A" uniqKey="Pallansch M">M. A. Pallansch</name></author><author><name sortKey="Weldon, W C" uniqKey="Weldon W">W. C. Weldon</name></author><author><name sortKey="Biggs, H M" uniqKey="Biggs H">H. M. Biggs</name></author><author><name sortKey="Uyeki, T M" uniqKey="Uyeki T">T. M. Uyeki</name></author><author><name sortKey="Pillai, S K" uniqKey="Pillai S">S. K. Pillai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ashburn, T T" uniqKey="Ashburn T">T. T. Ashburn</name></author><author><name sortKey="Thor, K B" uniqKey="Thor K">K. B. Thor</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pushpakom, S" uniqKey="Pushpakom S">S. Pushpakom</name></author><author><name sortKey="Iorio, F" uniqKey="Iorio F">F. Iorio</name></author><author><name sortKey="Eyers, P A" uniqKey="Eyers P">P. A. Eyers</name></author><author><name sortKey="Escott, K J" uniqKey="Escott K">K. J. Escott</name></author><author><name sortKey="Hopper, S" uniqKey="Hopper S">S. Hopper</name></author><author><name sortKey="Wells, A" uniqKey="Wells A">A. Wells</name></author><author><name sortKey="Doig, A" uniqKey="Doig A">A. Doig</name></author><author><name sortKey="Guilliams, T" uniqKey="Guilliams T">T. Guilliams</name></author><author><name sortKey="Latimer, J" uniqKey="Latimer J">J. Latimer</name></author><author><name sortKey="Mcnamee, C" uniqKey="Mcnamee C">C. McNamee</name></author><author><name sortKey="Norris, A" uniqKey="Norris A">A. Norris</name></author><author><name sortKey="Sanseau, P" uniqKey="Sanseau P">P. Sanseau</name></author><author><name sortKey="Cavalla, D" uniqKey="Cavalla D">D. Cavalla</name></author><author><name sortKey="Pirmohamed, M" uniqKey="Pirmohamed M">M. Pirmohamed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andrews, P" uniqKey="Andrews P">P. Andrews</name></author><author><name sortKey="Thyssen, J" uniqKey="Thyssen J">J. Thyssen</name></author><author><name sortKey="Lorke, D" uniqKey="Lorke D">D. Lorke</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Weinbach, E C" uniqKey="Weinbach E">E. C. Weinbach</name></author><author><name sortKey="Garbus, J" uniqKey="Garbus J">J. Garbus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y. Li</name></author><author><name sortKey="Li, P K" uniqKey="Li P">P.-K. Li</name></author><author><name sortKey="Roberts, M J" uniqKey="Roberts M">M. J. Roberts</name></author><author><name sortKey="Arend, R C" uniqKey="Arend R">R. C. Arend</name></author><author><name sortKey="Samant, R S" uniqKey="Samant R">R. S. Samant</name></author><author><name sortKey="Buchsbaum, D J" uniqKey="Buchsbaum D">D. J. Buchsbaum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Z" uniqKey="Li Z">Z. Li</name></author><author><name sortKey="Brecher, M" uniqKey="Brecher M">M. Brecher</name></author><author><name sortKey="Deng, Y Q" uniqKey="Deng Y">Y.-Q. Deng</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Sakamuru, S" uniqKey="Sakamuru S">S. Sakamuru</name></author><author><name sortKey="Liu, B" uniqKey="Liu B">B. Liu</name></author><author><name sortKey="Huang, R" uniqKey="Huang R">R. Huang</name></author><author><name sortKey="Koetzner, C A" uniqKey="Koetzner C">C. A. Koetzner</name></author><author><name sortKey="Allen, C A" uniqKey="Allen C">C. A. Allen</name></author><author><name sortKey="Jones, S A" uniqKey="Jones S">S. A. Jones</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Zhang, N N" uniqKey="Zhang N">N.-N. Zhang</name></author><author><name sortKey="Tian, M" uniqKey="Tian M">M. Tian</name></author><author><name sortKey="Gao, F" uniqKey="Gao F">F. Gao</name></author><author><name sortKey="Lin, Q" uniqKey="Lin Q">Q. Lin</name></author><author><name sortKey="Banavali, N" uniqKey="Banavali N">N. Banavali</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author><author><name sortKey="Boles, N" uniqKey="Boles N">N. Boles</name></author><author><name sortKey="Xia, M" uniqKey="Xia M">M. Xia</name></author><author><name sortKey="Kramer, L D" uniqKey="Kramer L">L. D. Kramer</name></author><author><name sortKey="Qin, C F" uniqKey="Qin C">C.-F. Qin</name></author><author><name sortKey="Li, H" uniqKey="Li H">H. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, W" uniqKey="Chen W">W. Chen</name></author><author><name sortKey="Mook, R A" uniqKey="Mook R">R. A. Mook</name></author><author><name sortKey="Premont, R T" uniqKey="Premont R">R. T. Premont</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Yang, Z" uniqKey="Yang Z">Z. Yang</name></author><author><name sortKey="Ding, C" uniqKey="Ding C">C. Ding</name></author><author><name sortKey="Chu, L" uniqKey="Chu L">L. Chu</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Terry, K" uniqKey="Terry K">K. Terry</name></author><author><name sortKey="Liu, H" uniqKey="Liu H">H. Liu</name></author><author><name sortKey="Shen, Q" uniqKey="Shen Q">Q. Shen</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Satoh, K" uniqKey="Satoh K">K. Satoh</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Chelluri, R" uniqKey="Chelluri R">R. Chelluri</name></author><author><name sortKey="Boufraqech, M" uniqKey="Boufraqech M">M. Boufraqech</name></author><author><name sortKey="Nilubol, N" uniqKey="Nilubol N">N. Nilubol</name></author><author><name sortKey="Patel, D" uniqKey="Patel D">D. Patel</name></author><author><name sortKey="Shen, M" uniqKey="Shen M">M. Shen</name></author><author><name sortKey="Kebebew, E" uniqKey="Kebebew E">E. Kebebew</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Osada, T" uniqKey="Osada T">T. Osada</name></author><author><name sortKey="Chen, M" uniqKey="Chen M">M. Chen</name></author><author><name sortKey="Yang, X Y" uniqKey="Yang X">X. Y. Yang</name></author><author><name sortKey="Spasojevic, I" uniqKey="Spasojevic I">I. Spasojevic</name></author><author><name sortKey="Vandeusen, J B" uniqKey="Vandeusen J">J. B. Vandeusen</name></author><author><name sortKey="Hsu, D" uniqKey="Hsu D">D. Hsu</name></author><author><name sortKey="Clary, B M" uniqKey="Clary B">B. M. Clary</name></author><author><name sortKey="Clay, T M" uniqKey="Clay T">T. M. Clay</name></author><author><name sortKey="Chen, W" uniqKey="Chen W">W. Chen</name></author><author><name sortKey="Morse, M A" uniqKey="Morse M">M. A. Morse</name></author><author><name sortKey="Lyerly, H K" uniqKey="Lyerly H">H. K. Lyerly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, J" uniqKey="Xu J">J. Xu</name></author><author><name sortKey="Pach N Iba Ez, M E" uniqKey="Pach N Iba Ez M">M. E. Pachón-Ibáñez</name></author><author><name sortKey="Cebrero Cangueiro, T" uniqKey="Cebrero Cangueiro T">T. Cebrero-Cangueiro</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Sanchez Cespedes, J" uniqKey="Sanchez Cespedes J">J. Sánchez-Céspedes</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fan, X" uniqKey="Fan X">X. Fan</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J. Xu</name></author><author><name sortKey="Files, M" uniqKey="Files M">M. Files</name></author><author><name sortKey="Cirillo, J D" uniqKey="Cirillo J">J. D. Cirillo</name></author><author><name sortKey="Endsley, J J" uniqKey="Endsley J">J. J. Endsley</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author><author><name sortKey="Endsley, M A" uniqKey="Endsley M">M. A. Endsley</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, Z" uniqKey="Sun Z">Z. Sun</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, M" uniqKey="Xu M">M. Xu</name></author><author><name sortKey="Lee, E M" uniqKey="Lee E">E. M. Lee</name></author><author><name sortKey="Wen, Z" uniqKey="Wen Z">Z. Wen</name></author><author><name sortKey="Cheng, Y" uniqKey="Cheng Y">Y. Cheng</name></author><author><name sortKey="Huang, W K" uniqKey="Huang W">W.-K. Huang</name></author><author><name sortKey="Qian, X" uniqKey="Qian X">X. Qian</name></author><author><name sortKey="Tcw, J" uniqKey="Tcw J">J. Tcw</name></author><author><name sortKey="Kouznetsova, J" uniqKey="Kouznetsova J">J. Kouznetsova</name></author><author><name sortKey="Ogden, S C" uniqKey="Ogden S">S. C. Ogden</name></author><author><name sortKey="Hammack, C" uniqKey="Hammack C">C. Hammack</name></author><author><name sortKey="Jacob, F" uniqKey="Jacob F">F. Jacob</name></author><author><name sortKey="Nguyen, H N" uniqKey="Nguyen H">H. N. Nguyen</name></author><author><name sortKey="Itkin, M" uniqKey="Itkin M">M. Itkin</name></author><author><name sortKey="Hanna, C" uniqKey="Hanna C">C. Hanna</name></author><author><name sortKey="Shinn, P" uniqKey="Shinn P">P. Shinn</name></author><author><name sortKey="Allen, C" uniqKey="Allen C">C. Allen</name></author><author><name sortKey="Michael, S G" uniqKey="Michael S">S. G. Michael</name></author><author><name sortKey="Simeonov, A" uniqKey="Simeonov A">A. Simeonov</name></author><author><name sortKey="Huang, W" uniqKey="Huang W">W. Huang</name></author><author><name sortKey="Christian, K M" uniqKey="Christian K">K. M. Christian</name></author><author><name sortKey="Goate, A" uniqKey="Goate A">A. Goate</name></author><author><name sortKey="Brennand, K J" uniqKey="Brennand K">K. J. Brennand</name></author><author><name sortKey="Huang, R" uniqKey="Huang R">R. Huang</name></author><author><name sortKey="Xia, M" uniqKey="Xia M">M. Xia</name></author><author><name sortKey="Ming, G L" uniqKey="Ming G">G.-l. Ming</name></author><author><name sortKey="Zheng, W" uniqKey="Zheng W">W. Zheng</name></author><author><name sortKey="Song, H" uniqKey="Song H">H. Song</name></author><author><name sortKey="Tang, H" uniqKey="Tang H">H. Tang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tao, H" uniqKey="Tao H">H. Tao</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author><author><name sortKey="Zeng, X" uniqKey="Zeng X">X. Zeng</name></author><author><name sortKey="Shulman, G I" uniqKey="Shulman G">G. I. Shulman</name></author><author><name sortKey="Jin, S" uniqKey="Jin S">S. Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, V M" uniqKey="Corman V">V. M. Corman</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name></author><author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D. Niemeyer</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Wu, C J" uniqKey="Wu C">C.-J. Wu</name></author><author><name sortKey="Jan, J T" uniqKey="Jan J">J.-T. Jan</name></author><author><name sortKey="Chen, C M" uniqKey="Chen C">C.-M. Chen</name></author><author><name sortKey="Hsieh, H P" uniqKey="Hsieh H">H.-P. Hsieh</name></author><author><name sortKey="Hwang, D R" uniqKey="Hwang D">D.-R. Hwang</name></author><author><name sortKey="Liu, H W" uniqKey="Liu H">H.-W. Liu</name></author><author><name sortKey="Liu, C Y" uniqKey="Liu C">C.-Y. Liu</name></author><author><name sortKey="Huang, H W" uniqKey="Huang H">H.-W. Huang</name></author><author><name sortKey="Chen, S C" uniqKey="Chen S">S.-C. Chen</name></author><author><name sortKey="Hong, C F" uniqKey="Hong C">C.-F. Hong</name></author><author><name sortKey="Lin, R K" uniqKey="Lin R">R.-K. Lin</name></author><author><name sortKey="Chao, Y S" uniqKey="Chao Y">Y.-S. Chao</name></author><author><name sortKey="Hsu, J T A" uniqKey="Hsu J">J. T. A. Hsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wen, C C" uniqKey="Wen C">C.-C. Wen</name></author><author><name sortKey="Kuo, Y H" uniqKey="Kuo Y">Y.-H. Kuo</name></author><author><name sortKey="Jan, J T" uniqKey="Jan J">J.-T. Jan</name></author><author><name sortKey="Liang, P H" uniqKey="Liang P">P.-H. Liang</name></author><author><name sortKey="Wang, S Y" uniqKey="Wang S">S.-Y. Wang</name></author><author><name sortKey="Liu, H G" uniqKey="Liu H">H.-G. Liu</name></author><author><name sortKey="Lee, C K" uniqKey="Lee C">C.-K. Lee</name></author><author><name sortKey="Chang, S T" uniqKey="Chang S">S.-T. Chang</name></author><author><name sortKey="Kuo, C J" uniqKey="Kuo C">C.-J. Kuo</name></author><author><name sortKey="Lee, S S" uniqKey="Lee S">S.-S. Lee</name></author><author><name sortKey="Hou, C C" uniqKey="Hou C">C.-C. Hou</name></author><author><name sortKey="Hsiao, P W" uniqKey="Hsiao P">P.-W. Hsiao</name></author><author><name sortKey="Chien, S C" uniqKey="Chien S">S.-C. Chien</name></author><author><name sortKey="Shyur, L F" uniqKey="Shyur L">L.-F. Shyur</name></author><author><name sortKey="Yang, N S" uniqKey="Yang N">N.-S. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anand, K" uniqKey="Anand K">K. Anand</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Wadhwani, P" uniqKey="Wadhwani P">P. Wadhwani</name></author><author><name sortKey="Mesters, J R" uniqKey="Mesters J">J. R. Mesters</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author><author><name sortKey="Yang, M" uniqKey="Yang M">M. Yang</name></author><author><name sortKey="Ding, Y" uniqKey="Ding Y">Y. Ding</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Lou, Z" uniqKey="Lou Z">Z. Lou</name></author><author><name sortKey="Zhou, Z" uniqKey="Zhou Z">Z. Zhou</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L. Sun</name></author><author><name sortKey="Mo, L" uniqKey="Mo L">L. Mo</name></author><author><name sortKey="Ye, S" uniqKey="Ye S">S. Ye</name></author><author><name sortKey="Pang, H" uniqKey="Pang H">H. Pang</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G. F. Gao</name></author><author><name sortKey="Anand, K" uniqKey="Anand K">K. Anand</name></author><author><name sortKey="Bartlam, M" uniqKey="Bartlam M">M. Bartlam</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author><author><name sortKey="Rao, Z" uniqKey="Rao Z">Z. Rao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chou, K C" uniqKey="Chou K">K.-C. Chou</name></author><author><name sortKey="Wei, D Q" uniqKey="Wei D">D.-Q. Wei</name></author><author><name sortKey="Zhong, W Z" uniqKey="Zhong W">W.-Z. Zhong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shie, J J" uniqKey="Shie J">J.-J. Shie</name></author><author><name sortKey="Fang, J M" uniqKey="Fang J">J.-M. Fang</name></author><author><name sortKey="Kuo, C J" uniqKey="Kuo C">C.-J. Kuo</name></author><author><name sortKey="Kuo, T H" uniqKey="Kuo T">T.-H. Kuo</name></author><author><name sortKey="Liang, P H" uniqKey="Liang P">P.-H. Liang</name></author><author><name sortKey="Huang, H J" uniqKey="Huang H">H.-J. Huang</name></author><author><name sortKey="Yang, W B" uniqKey="Yang W">W.-B. Yang</name></author><author><name sortKey="Lin, C H" uniqKey="Lin C">C.-H. Lin</name></author><author><name sortKey="Chen, J L" uniqKey="Chen J">J.-L. Chen</name></author><author><name sortKey="Wu, Y T" uniqKey="Wu Y">Y.-T. Wu</name></author><author><name sortKey="Wong, C H" uniqKey="Wong C">C.-H. Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gassen, N C" uniqKey="Gassen N">N. C. Gassen</name></author><author><name sortKey="Niemeyer, D" uniqKey="Niemeyer D">D. Niemeyer</name></author><author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name></author><author><name sortKey="Corman, V M" uniqKey="Corman V">V. M. Corman</name></author><author><name sortKey="Martinelli, S" uniqKey="Martinelli S">S. Martinelli</name></author><author><name sortKey="Gassen, A" uniqKey="Gassen A">A. Gassen</name></author><author><name sortKey="Hafner, K" uniqKey="Hafner K">K. Hafner</name></author><author><name sortKey="Papies, J" uniqKey="Papies J">J. Papies</name></author><author><name sortKey="Mosbauer, K" uniqKey="Mosbauer K">K. Mosbauer</name></author><author><name sortKey="Zellner, A" uniqKey="Zellner A">A. Zellner</name></author><author><name sortKey="Zannas, A S" uniqKey="Zannas A">A. S. Zannas</name></author><author><name sortKey="Herrmann, A" uniqKey="Herrmann A">A. Herrmann</name></author><author><name sortKey="Holsboer, F" uniqKey="Holsboer F">F. Holsboer</name></author><author><name sortKey="Brack Werner, R" uniqKey="Brack Werner R">R. Brack-Werner</name></author><author><name sortKey="Boshart, M" uniqKey="Boshart M">M. Boshart</name></author><author><name sortKey="Muller Myhsok, B" uniqKey="Muller Myhsok B">B. Muller-Myhsok</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name></author><author><name sortKey="Muller, M A" uniqKey="Muller M">M. A. Muller</name></author><author><name sortKey="Rein, T" uniqKey="Rein T">T. Rein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mlakar, J" uniqKey="Mlakar J">J. Mlakar</name></author><author><name sortKey="Korva, M" uniqKey="Korva M">M. Korva</name></author><author><name sortKey="Tul, N" uniqKey="Tul N">N. Tul</name></author><author><name sortKey="Popovi, M" uniqKey="Popovi M">M. Popović</name></author><author><name sortKey="Poljsak Prijatelj, M" uniqKey="Poljsak Prijatelj M">M. Poljšak-Prijatelj</name></author><author><name sortKey="Mraz, J" uniqKey="Mraz J">J. Mraz</name></author><author><name sortKey="Kolenc, M" uniqKey="Kolenc M">M. Kolenc</name></author><author><name sortKey="Resman Rus, K" uniqKey="Resman Rus K">K. Resman Rus</name></author><author><name sortKey="Vesnaver Vipotnik, T" uniqKey="Vesnaver Vipotnik T">T. Vesnaver Vipotnik</name></author><author><name sortKey="Fabjan Vodusek, V" uniqKey="Fabjan Vodusek V">V. Fabjan Vodušek</name></author><author><name sortKey="Vizjak, A" uniqKey="Vizjak A">A. Vizjak</name></author><author><name sortKey="Pizem, J" uniqKey="Pizem J">J. Pižem</name></author><author><name sortKey="Petrovec, M" uniqKey="Petrovec M">M. Petrovec</name></author><author><name sortKey="Avsi Upanc, T" uniqKey="Avsi Upanc T">T. Avšič Županc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rasmussen, S A" uniqKey="Rasmussen S">S. A. Rasmussen</name></author><author><name sortKey="Jamieson, D J" uniqKey="Jamieson D">D. J. Jamieson</name></author><author><name sortKey="Honein, M A" uniqKey="Honein M">M. A. Honein</name></author><author><name sortKey="Petersen, L R" uniqKey="Petersen L">L. R. Petersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Petersen, E" uniqKey="Petersen E">E. Petersen</name></author><author><name sortKey="Wilson, M E" uniqKey="Wilson M">M. E. Wilson</name></author><author><name sortKey="Touch, S" uniqKey="Touch S">S. Touch</name></author><author><name sortKey="Mccloskey, B" uniqKey="Mccloskey B">B. McCloskey</name></author><author><name sortKey="Mwaba, P" uniqKey="Mwaba P">P. Mwaba</name></author><author><name sortKey="Bates, M" uniqKey="Bates M">M. Bates</name></author><author><name sortKey="Dar, O" uniqKey="Dar O">O. Dar</name></author><author><name sortKey="Mattes, F" uniqKey="Mattes F">F. Mattes</name></author><author><name sortKey="Kidd, M" uniqKey="Kidd M">M. Kidd</name></author><author><name sortKey="Ippolito, G" uniqKey="Ippolito G">G. Ippolito</name></author><author><name sortKey="Azhar, E I" uniqKey="Azhar E">E. I. Azhar</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cao Lormeau, V M" uniqKey="Cao Lormeau V">V.-M. Cao-Lormeau</name></author><author><name sortKey="Blake, A" uniqKey="Blake A">A. Blake</name></author><author><name sortKey="Mons, S" uniqKey="Mons S">S. Mons</name></author><author><name sortKey="Lastere, S" uniqKey="Lastere S">S. Lastère</name></author><author><name sortKey="Roche, C" uniqKey="Roche C">C. Roche</name></author><author><name sortKey="Vanhomwegen, J" uniqKey="Vanhomwegen J">J. Vanhomwegen</name></author><author><name sortKey="Dub, T" uniqKey="Dub T">T. Dub</name></author><author><name sortKey="Baudouin, L" uniqKey="Baudouin L">L. Baudouin</name></author><author><name sortKey="Teissier, A" uniqKey="Teissier A">A. Teissier</name></author><author><name sortKey="Larre, P" uniqKey="Larre P">P. Larre</name></author><author><name sortKey="Vial, A L" uniqKey="Vial A">A.-L. Vial</name></author><author><name sortKey="Decam, C" uniqKey="Decam C">C. Decam</name></author><author><name sortKey="Choumet, V" uniqKey="Choumet V">V. Choumet</name></author><author><name sortKey="Halstead, S K" uniqKey="Halstead S">S. K. Halstead</name></author><author><name sortKey="Willison, H J" uniqKey="Willison H">H. J. Willison</name></author><author><name sortKey="Musset, L" uniqKey="Musset L">L. Musset</name></author><author><name sortKey="Manuguerra, J C" uniqKey="Manuguerra J">J.-C. Manuguerra</name></author><author><name sortKey="Despres, P" uniqKey="Despres P">P. Despres</name></author><author><name sortKey="Fournier, E" uniqKey="Fournier E">E. Fournier</name></author><author><name sortKey="Mallet, H P" uniqKey="Mallet H">H.-P. Mallet</name></author><author><name sortKey="Musso, D" uniqKey="Musso D">D. Musso</name></author><author><name sortKey="Fontanet, A" uniqKey="Fontanet A">A. Fontanet</name></author><author><name sortKey="Neil, J" uniqKey="Neil J">J. Neil</name></author><author><name sortKey="Ghawche, F" uniqKey="Ghawche F">F. Ghawché</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pantaleao Fontes, C A" uniqKey="Pantaleao Fontes C">C. A. Pantaleao Fontes</name></author><author><name sortKey="Damas Dos Santos, A A S M" uniqKey="Damas Dos Santos A">A. A. S. M. Damas dos Santos</name></author><author><name sortKey="Marchiori, E" uniqKey="Marchiori E">E. Marchiori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chambers, T J" uniqKey="Chambers T">T. J. Chambers</name></author><author><name sortKey="Grakoui, A" uniqKey="Grakoui A">A. Grakoui</name></author><author><name sortKey="Rice, C M" uniqKey="Rice C">C. M. Rice</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falgout, B" uniqKey="Falgout B">B. Falgout</name></author><author><name sortKey="Pethel, M" uniqKey="Pethel M">M. Pethel</name></author><author><name sortKey="Zhang, Y M" uniqKey="Zhang Y">Y. M. Zhang</name></author><author><name sortKey="Lai, C J" uniqKey="Lai C">C. J. Lai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, D" uniqKey="Luo D">D. Luo</name></author><author><name sortKey="Vasudevan, S G" uniqKey="Vasudevan S">S. G. Vasudevan</name></author><author><name sortKey="Lescar, J" uniqKey="Lescar J">J. Lescar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fang, J E" uniqKey="Fang J">J. e. Fang</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L. Sun</name></author><author><name sortKey="Peng, G" uniqKey="Peng G">G. Peng</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J. Xu</name></author><author><name sortKey="Zhou, R" uniqKey="Zhou R">R. Zhou</name></author><author><name sortKey="Cao, S" uniqKey="Cao S">S. Cao</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Song, Y" uniqKey="Song Y">Y. Song</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Stachulski, A V" uniqKey="Stachulski A">A. V. Stachulski</name></author><author><name sortKey="Pidathala, C" uniqKey="Pidathala C">C. Pidathala</name></author><author><name sortKey="Row, E C" uniqKey="Row E">E. C. Row</name></author><author><name sortKey="Sharma, R" uniqKey="Sharma R">R. Sharma</name></author><author><name sortKey="Berry, N G" uniqKey="Berry N">N. G. Berry</name></author><author><name sortKey="Lawrenson, A S" uniqKey="Lawrenson A">A. S. Lawrenson</name></author><author><name sortKey="Moores, S L" uniqKey="Moores S">S. L. Moores</name></author><author><name sortKey="Iqbal, M" uniqKey="Iqbal M">M. Iqbal</name></author><author><name sortKey="Bentley, J" uniqKey="Bentley J">J. Bentley</name></author><author><name sortKey="Allman, S A" uniqKey="Allman S">S. A. Allman</name></author><author><name sortKey="Edwards, G" uniqKey="Edwards G">G. Edwards</name></author><author><name sortKey="Helm, A" uniqKey="Helm A">A. Helm</name></author><author><name sortKey="Hellier, J" uniqKey="Hellier J">J. Hellier</name></author><author><name sortKey="Korba, B E" uniqKey="Korba B">B. E. Korba</name></author><author><name sortKey="Semple, J E" uniqKey="Semple J">J. E. Semple</name></author><author><name sortKey="Rossignol, J F" uniqKey="Rossignol J">J.-F. Rossignol</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Korba, B E" uniqKey="Korba B">B. E. Korba</name></author><author><name sortKey="Elazar, M" uniqKey="Elazar M">M. Elazar</name></author><author><name sortKey="Lui, P" uniqKey="Lui P">P. Lui</name></author><author><name sortKey="Rossignol, J F" uniqKey="Rossignol J">J.-F. Rossignol</name></author><author><name sortKey="Glenn, J S" uniqKey="Glenn J">J. S. Glenn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yon, C" uniqKey="Yon C">C. Yon</name></author><author><name sortKey="Viswanathan, P" uniqKey="Viswanathan P">P. Viswanathan</name></author><author><name sortKey="Rossignol, J F" uniqKey="Rossignol J">J. F. Rossignol</name></author><author><name sortKey="Korba, B" uniqKey="Korba B">B. Korba</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Carvalho, L P" uniqKey="De Carvalho L">L. P. de Carvalho</name></author><author><name sortKey="Darby, C M" uniqKey="Darby C">C. M. Darby</name></author><author><name sortKey="Rhee, K Y" uniqKey="Rhee K">K. Y. Rhee</name></author><author><name sortKey="Nathan, C" uniqKey="Nathan C">C. Nathan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Madrid, P B" uniqKey="Madrid P">P. B. Madrid</name></author><author><name sortKey="Panchal, R G" uniqKey="Panchal R">R. G. Panchal</name></author><author><name sortKey="Warren, T K" uniqKey="Warren T">T. K. Warren</name></author><author><name sortKey="Shurtleff, A C" uniqKey="Shurtleff A">A. C. Shurtleff</name></author><author><name sortKey="Endsley, A N" uniqKey="Endsley A">A. N. Endsley</name></author><author><name sortKey="Green, C E" uniqKey="Green C">C. E. Green</name></author><author><name sortKey="Kolokoltsov, A" uniqKey="Kolokoltsov A">A. Kolokoltsov</name></author><author><name sortKey="Davey, R" uniqKey="Davey R">R. Davey</name></author><author><name sortKey="Manger, I D" uniqKey="Manger I">I. D. Manger</name></author><author><name sortKey="Gilfillan, L" uniqKey="Gilfillan L">L. Gilfillan</name></author><author><name sortKey="Bavari, S" uniqKey="Bavari S">S. Bavari</name></author><author><name sortKey="Tanga, M J" uniqKey="Tanga M">M. J. Tanga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacobs, S E" uniqKey="Jacobs S">S. E. Jacobs</name></author><author><name sortKey="Lamson, D M" uniqKey="Lamson D">D. M. Lamson</name></author><author><name sortKey="St George, K" uniqKey="St George K">K. St George</name></author><author><name sortKey="Walsh, T J" uniqKey="Walsh T">T. J. Walsh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jurgeit, A" uniqKey="Jurgeit A">A. Jurgeit</name></author><author><name sortKey="Mcdowell, R" uniqKey="Mcdowell R">R. McDowell</name></author><author><name sortKey="Moese, S" uniqKey="Moese S">S. Moese</name></author><author><name sortKey="Meldrum, E" uniqKey="Meldrum E">E. Meldrum</name></author><author><name sortKey="Schwendener, R" uniqKey="Schwendener R">R. Schwendener</name></author><author><name sortKey="Greber, U F" uniqKey="Greber U">U. F. Greber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Y M" uniqKey="Wang Y">Y.-M. Wang</name></author><author><name sortKey="Lu, J W" uniqKey="Lu J">J.-W. Lu</name></author><author><name sortKey="Lin, C C" uniqKey="Lin C">C.-C. Lin</name></author><author><name sortKey="Chin, Y F" uniqKey="Chin Y">Y.-F. Chin</name></author><author><name sortKey="Wu, T Y" uniqKey="Wu T">T.-Y. Wu</name></author><author><name sortKey="Lin, L I" uniqKey="Lin L">L.-I. Lin</name></author><author><name sortKey="Lai, Z Z" uniqKey="Lai Z">Z.-Z. Lai</name></author><author><name sortKey="Kuo, S C" uniqKey="Kuo S">S.-C. Kuo</name></author><author><name sortKey="Ho, Y J" uniqKey="Ho Y">Y.-J. Ho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marrugal Lorenzo, J A" uniqKey="Marrugal Lorenzo J">J. A. Marrugal-Lorenzo</name></author><author><name sortKey="Serna Gallego, A" uniqKey="Serna Gallego A">A. Serna-Gallego</name></author><author><name sortKey="Berastegui Cabrera, J" uniqKey="Berastegui Cabrera J">J. Berastegui-Cabrera</name></author><author><name sortKey="Pach N, J" uniqKey="Pach N J">J. Pachón</name></author><author><name sortKey="Sanchez Cespedes, J" uniqKey="Sanchez Cespedes J">J. Sánchez-Céspedes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kutok, J L" uniqKey="Kutok J">J. L. Kutok</name></author><author><name sortKey="Wang, F" uniqKey="Wang F">F. Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, L" uniqKey="Huang L">L. Huang</name></author><author><name sortKey="Yang, M" uniqKey="Yang M">M. Yang</name></author><author><name sortKey="Yuan, Y" uniqKey="Yuan Y">Y. Yuan</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Kuang, E" uniqKey="Kuang E">E. Kuang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, W E" uniqKey="Jones W">W. E. Jones</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Chang, Y W" uniqKey="Chang Y">Y.-W. Chang</name></author><author><name sortKey="Yeh, T K" uniqKey="Yeh T">T.-K. Yeh</name></author><author><name sortKey="Lin, K T" uniqKey="Lin K">K.-T. Lin</name></author><author><name sortKey="Chen, W C" uniqKey="Chen W">W.-C. Chen</name></author><author><name sortKey="Yao, H T" uniqKey="Yao H">H.-T. Yao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xu, J" uniqKey="Xu J">J. Xu</name></author><author><name sortKey="Berastegui Cabrera, J" uniqKey="Berastegui Cabrera J">J. Berastegui-Cabrera</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author><author><name sortKey="Pach N, J" uniqKey="Pach N J">J. Pachón</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author><author><name sortKey="Sanchez Cespedes, J" uniqKey="Sanchez Cespedes J">J. Sanchez-Cespedes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mook, R A" uniqKey="Mook R">R. A. Mook</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J. Wang</name></author><author><name sortKey="Ren, X R" uniqKey="Ren X">X.-R. Ren</name></author><author><name sortKey="Chen, M" uniqKey="Chen M">M. Chen</name></author><author><name sortKey="Spasojevic, I" uniqKey="Spasojevic I">I. Spasojevic</name></author><author><name sortKey="Barak, L S" uniqKey="Barak L">L. S. Barak</name></author><author><name sortKey="Lyerly, H K" uniqKey="Lyerly H">H. K. Lyerly</name></author><author><name sortKey="Chen, W" uniqKey="Chen W">W. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barbosa, E J" uniqKey="Barbosa E">E. J. Barbosa</name></author><author><name sortKey="Lobenberg, R" uniqKey="Lobenberg R">R. Löbenberg</name></author><author><name sortKey="De Araujo, G L B" uniqKey="De Araujo G">G. L. B. de Araujo</name></author><author><name sortKey="Bou Chacra, N A" uniqKey="Bou Chacra N">N. A. Bou-Chacra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Costabile, G" uniqKey="Costabile G">G. Costabile</name></author><author><name sortKey="D Ngelo, I" uniqKey="D Ngelo I">I. d’Angelo</name></author><author><name sortKey="Rampioni, G" uniqKey="Rampioni G">G. Rampioni</name></author><author><name sortKey="Bondi, R" uniqKey="Bondi R">R. Bondì</name></author><author><name sortKey="Pompili, B" uniqKey="Pompili B">B. Pompili</name></author><author><name sortKey="Ascenzioni, F" uniqKey="Ascenzioni F">F. Ascenzioni</name></author><author><name sortKey="Mitidieri, E" uniqKey="Mitidieri E">E. Mitidieri</name></author><author><name sortKey="D Mmanuele Di Villa Bianca, R" uniqKey="D Mmanuele Di Villa Bianca R">R. d’Emmanuele di Villa Bianca</name></author><author><name sortKey="Sorrentino, R" uniqKey="Sorrentino R">R. Sorrentino</name></author><author><name sortKey="Miro, A" uniqKey="Miro A">A. Miro</name></author><author><name sortKey="Quaglia, F" uniqKey="Quaglia F">F. Quaglia</name></author><author><name sortKey="Imperi, F" uniqKey="Imperi F">F. Imperi</name></author><author><name sortKey="Leoni, L" uniqKey="Leoni L">L. Leoni</name></author><author><name sortKey="Ungaro, F" uniqKey="Ungaro F">F. Ungaro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, C K" uniqKey="Lin C">C.-K. Lin</name></author><author><name sortKey="Bai, M Y" uniqKey="Bai M">M.-Y. Bai</name></author><author><name sortKey="Hu, T M" uniqKey="Hu T">T.-M. Hu</name></author><author><name sortKey="Wang, Y C" uniqKey="Wang Y">Y.-C. Wang</name></author><author><name sortKey="Chao, T K" uniqKey="Chao T">T.-K. Chao</name></author><author><name sortKey="Weng, S J" uniqKey="Weng S">S.-J. Weng</name></author><author><name sortKey="Huang, R L" uniqKey="Huang R">R.-L. Huang</name></author><author><name sortKey="Su, P H" uniqKey="Su P">P.-H. Su</name></author><author><name sortKey="Lai, H C" uniqKey="Lai H">H.-C. Lai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wrapp, D" uniqKey="Wrapp D">D. Wrapp</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="Goldsmith, J A" uniqKey="Goldsmith J">J. A. Goldsmith</name></author><author><name sortKey="Hsieh, C L" uniqKey="Hsieh C">C.-L. Hsieh</name></author><author><name sortKey="Abiona, O" uniqKey="Abiona O">O. Abiona</name></author><author><name sortKey="Graham, B S" uniqKey="Graham B">B. S. Graham</name></author><author><name sortKey="Mclellan, J S" uniqKey="Mclellan J">J. S. McLellan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cohen, J" uniqKey="Cohen J">J. Cohen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, G" uniqKey="Li G">G. Li</name></author><author><name sortKey="De Clercq, E" uniqKey="De Clercq E">E. De Clercq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author><author><name sortKey="Cao, R" uniqKey="Cao R">R. Cao</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="Xu, M" uniqKey="Xu M">M. Xu</name></author><author><name sortKey="Shi, Z" uniqKey="Shi Z">Z. Shi</name></author><author><name sortKey="Hu, Z" uniqKey="Hu Z">Z. Hu</name></author><author><name sortKey="Zhong, W" uniqKey="Zhong W">W. Zhong</name></author><author><name sortKey="Xiao, G" uniqKey="Xiao G">G. Xiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, P" uniqKey="Zhou P">P. Zhou</name></author><author><name sortKey="Yang, X L" uniqKey="Yang X">X.-L. Yang</name></author><author><name sortKey="Wang, X G" uniqKey="Wang X">X.-G. Wang</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B. Hu</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L. Zhang</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Si, H R" uniqKey="Si H">H.-R. Si</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y. Zhu</name></author><author><name sortKey="Li, B" uniqKey="Li B">B. Li</name></author><author><name sortKey="Huang, C L" uniqKey="Huang C">C.-L. Huang</name></author><author><name sortKey="Chen, H D" uniqKey="Chen H">H.-D. Chen</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Luo, Y" uniqKey="Luo Y">Y. Luo</name></author><author><name sortKey="Guo, H" uniqKey="Guo H">H. Guo</name></author><author><name sortKey="Jiang, R D" uniqKey="Jiang R">R.-D. Jiang</name></author><author><name sortKey="Liu, M Q" uniqKey="Liu M">M.-Q. Liu</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="Shen, X R" uniqKey="Shen X">X.-R. Shen</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Zheng, X S" uniqKey="Zheng X">X.-S. Zheng</name></author><author><name sortKey="Zhao, K" uniqKey="Zhao K">K. Zhao</name></author><author><name sortKey="Chen, Q J" uniqKey="Chen Q">Q.-J. Chen</name></author><author><name sortKey="Deng, F" uniqKey="Deng F">F. Deng</name></author><author><name sortKey="Liu, L L" uniqKey="Liu L">L.-L. Liu</name></author><author><name sortKey="Yan, B" uniqKey="Yan B">B. Yan</name></author><author><name sortKey="Zhan, F X" uniqKey="Zhan F">F.-X. Zhan</name></author><author><name sortKey="Wang, Y Y" uniqKey="Wang Y">Y.-Y. Wang</name></author><author><name sortKey="Xiao, G F" uniqKey="Xiao G">G.-F. Xiao</name></author><author><name sortKey="Shi, Z L" uniqKey="Shi Z">Z.-L. Shi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article" xml:lang="EN"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">ACS Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">ACS Infect Dis</journal-id><journal-id journal-id-type="publisher-id">id</journal-id><journal-id journal-id-type="coden">aidcbc</journal-id><journal-title-group><journal-title>ACS Infectious Diseases</journal-title></journal-title-group><issn pub-type="epub">2373-8227</issn><publisher><publisher-name>American Chemical Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32125140</article-id><article-id pub-id-type="pmc">7098069</article-id><article-id pub-id-type="doi">10.1021/acsinfecdis.0c00052</article-id><article-categories><subj-group><subject>Review</subject></subj-group></article-categories><title-group><article-title>Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic
Potential</article-title></title-group><contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Xu</surname><given-names>Jimin</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath2"><name><surname>Shi</surname><given-names>Pei-Yong</given-names></name><xref rid="aff1" ref-type="aff">‡</xref><xref rid="aff1" ref-type="aff">§</xref></contrib><contrib contrib-type="author" id="ath3"><name><surname>Li</surname><given-names>Hongmin</given-names></name><xref rid="aff2" ref-type="aff">∥</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath4"><name><surname>Zhou</surname><given-names>Jia</given-names></name><xref rid="cor1" ref-type="other">*</xref><xref rid="aff1" ref-type="aff">†</xref><xref rid="aff1" ref-type="aff">§</xref></contrib><aff id="aff1"><sup>†</sup>Chemical Biology Program, Department of Pharmacology and Toxicology,<sup>‡</sup>Department of Biochemistry and Molecular Biology, and<sup>§</sup>Sealy Center for Structural Biology & Molecular Biophysics,<institution>University of Texas Medical Branch</institution>, Galveston, Texas 77555,<country>United States</country></aff><aff id="aff2"><label>∥</label><institution>Wadsworth Center, New York State Department of Health</institution>, 120 New Scotland Avenue, Albany, New York 12208,<country>United States</country></aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>E-mail: <email>jizhou@utmb.edu</email>. Tel: <phone>(409)
772-9748</phone>.</corresp></author-notes><pub-date pub-type="epub"><day>03</day><month>03</month><year>2020</year></pub-date><elocation-id>acsinfecdis.0c00052</elocation-id><history><date date-type="received"><day>04</day><month>02</month><year>2020</year></date></history><permissions><copyright-statement>Copyright © 2020 American Chemical Society</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>American Chemical Society</copyright-holder><license license-type="open-access"><license-p>This article is made available via the PMC Open Access Subset 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 the duration of the World Health Organization
(WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract><p content-type="toc-graphic"><graphic xlink:href="id0c00052_0003" id="ab-tgr1"></graphic></p><p>The recent outbreak of coronavirus disease 2019 (COVID-19) highlights an urgent need
for therapeutics. Through a series of drug repurposing screening campaigns, niclosamide,
an FDA-approved anthelminthic drug, was found to be effective against various viral
infections with nanomolar to micromolar potency such as SARS-CoV, MERS-CoV, ZIKV, HCV,
and human adenovirus, indicating its potential as an antiviral agent. In this brief
review, we summarize the broad antiviral activity of niclosamide and highlight its
potential clinical use in the treatment of COVID-19.</p></abstract><kwd-group><kwd>niclosamide</kwd><kwd>broad antiviral agents</kwd><kwd>coronavirus</kwd><kwd>SARS-CoV</kwd><kwd>MERS-CoV</kwd><kwd>SARS-CoV-2 (COVID-19)</kwd><kwd>flavivirus</kwd><kwd>Zika virus</kwd><kwd>Ebola virus</kwd><kwd>human adenovirus</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>document-id-old-9</meta-name><meta-value>id0c00052</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>id0c00052</meta-value></custom-meta><custom-meta><meta-name>ccc-price</meta-name><meta-value></meta-value></custom-meta></custom-meta-group></article-meta><notes id="notes-d1e21-autogenerated"><fn-group><fn fn-type="" id="d30e140"><p>This article is made available for a limited time sponsored by ACS under the <ext-link ext-link-type="uri" xlink:href="http://pubs.acs.org/page/policy/freetoread/index.html">ACS Free to Read
License</ext-link>, which permits copying and redistribution of the article for
non-commercial scholarly purposes.</p></fn></fn-group></notes></front><body><p id="sec1">The recent outbreak of coronavirus disease 2019 (COVID-19) first detected in Wuhan, China,
was caused by a novel betacoronavirus, which was named SARS-CoV-2 (a.k.a. 2019-nCoV) by the
International Committee on Taxonomy of Viruses.<sup><xref ref-type="bibr" rid="ref1">1</xref></sup> Coronaviruses (CoVs) are
enveloped and positive-sense single-stranded RNA viruses belonging to the family
<italic>Coronaviridae</italic> within the order <italic>Nidovirales</italic>. Many
coronaviruses infect humans and other mammalian hosts. Coronavirus can be divided into four
genera (alpha, beta, gamma, and delta), of which alpha and beta coronaviruses are known to
infect humans.<sup><xref ref-type="bibr" rid="ref2">2</xref></sup> Human coronavirus infections are typically mild and
rarely associated with severe diseases. However, the epidemics of Middle East respiratory
syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV)
caused alarming morbidity and mortality.<sup><xref ref-type="bibr" rid="ref3">3</xref></sup> While coronaviruses are often
zoonotic, person-to-person transmission has been confirmed for SARS-CoV-2, similar to
MERS-CoV and SARS-CoV.<sup><xref ref-type="bibr" rid="ref4">4</xref></sup> As of March 5, 2020, there are more than
95 333 confirmed cases of COVID-19 and at least 3282 reported deaths, indicating that
it is a severe public health threat.<sup><xref ref-type="bibr" rid="ref5">5</xref></sup> There is no clinically approved
antiviral for coronavirus therapy.<sup><xref ref-type="bibr" rid="ref6">6</xref></sup> Although remdesivir, an experimental
antiviral drug candidate by Gilead currently advanced into human clinical trials to treat
COVID-19 in both China and the U.S., was reported to improve patient outcomes in a recent
study,<sup><xref ref-type="bibr" rid="ref7">7</xref></sup> it is still critical and urgent to search for other effective
inhibitors for the potential treatment of COVID-19.</p><p>Drug repurposing screens have emerged as an attractive strategy to accelerate new drug
discovery and development. This strategy offers various advantages over <italic>de
novo</italic> drug discovery featured with key benefits including reduced time, cost, and
risk as well as the unique means for safer and more effective drugs to be accessed by
patients.<sup><xref ref-type="bibr" rid="ref8">8</xref>,<xref ref-type="bibr" rid="ref9">9</xref></sup>Niclosamide is an FDA-approved anthelminthic drug that has been widely used in humans to
treat tapeworm infections for several decades and is currently listed on the World Health
Organization’s list of essential medicines.<sup><xref ref-type="bibr" rid="ref10">10</xref>,<xref ref-type="bibr" rid="ref11">11</xref></sup> Niclosamide exerts its anticestodal effect by
inhibiting oxidative phosphorylation and stimulating adenosine triphosphatase activity in
the mitochondria.<sup><xref ref-type="bibr" rid="ref12">12</xref></sup> Over the past several years, niclosamide has been
identified as a multifunctional drug via drug repurposing screens. It can regulate multiple
signaling pathways and biological processes including Wnt/β-catenin, mTORC1, STAT3,
NF-κB, Notch, NS2B-NS3 interaction, and pH,<sup><xref ref-type="bibr" rid="ref13">13</xref>,<xref ref-type="bibr" rid="ref14">14</xref></sup> indicating its potential to treat other human
conditions<sup><xref ref-type="bibr" rid="ref15">15</xref></sup> such as cancer,<sup><xref ref-type="bibr" rid="ref16">16</xref>−<xref ref-type="bibr" rid="ref18">18</xref></sup> bacterial and viral infections,<sup><xref ref-type="bibr" rid="ref19">19</xref>−<xref ref-type="bibr" rid="ref22">22</xref></sup> and metabolic
diseases.<sup><xref ref-type="bibr" rid="ref23">23</xref></sup> These broad biological activities of niclosamide including
relevant cell signaling pathways were briefly reviewed by Chen et al.<sup><xref ref-type="bibr" rid="ref15">15</xref></sup>In this short review, we focus on summarizing the broad antiviral activities of niclosamide
(<xref rid="fig1" ref-type="fig">Figure <xref rid="fig1" ref-type="fig">1</xref></xref>) and highlighting its therapeutic
potential in combating COVID-19.</p><fig id="fig1" position="float"><label>Figure 1</label><caption><p>Niclosamide has great potential in being repurposed to treat a variety of viral
infections, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle
East respiratory syndrome coronavirus (MERS-CoV), Zika virus (ZIKV), Japanese
encephalitis virus (JEV), hepatitis C virus (HCV), Ebola virus (EBOV), human
rhinoviruses (HRVs), Chikungunya virus (CHIKV), human adenovirus (HAdV), and
Epstein–Barr virus (EBV). We envision that this broad spectrum of antival
activities may offer the therapeutic potential to be extended to combat fast-spreading
coronavirus disease 2019 (COVID-19), given its inexpensive and low <italic>in
vivo</italic> toxicity profile as an FDA-approved drug in clinical use.</p></caption><graphic xlink:href="id0c00052_0001" id="gr1" position="float"></graphic></fig><sec id="sec2"><title>Niclosamide and Viral Infections</title><sec id="sec2.1"><title>Niclosamide and Coronavirus</title><p>Coronaviruses are a group of enveloped and nonsegmented positive-sense RNA viruses with
very large genome size ranging from approximately 27 to 34 kb. Infections with human
strains HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 usually cause mild, self-limiting
respiratory infections such as the common cold.<sup><xref ref-type="bibr" rid="ref2">2</xref>,<xref ref-type="bibr" rid="ref24">24</xref></sup> Nevertheless, in the past 17 years, three beta
coronaviruses (SARS-CoV, MERS-CoV, and this year’s SARS-CoV-2) have caused severe
human disease pandemics associated with high morbidity and mortality. The outbreak of SARS
in southern China between November 2002 and July 2003 eventually resulted in 8098
confirmed cases and 774 deaths reported in 17 countries with a mortality rate of 9%, while
MERS, first identified in Saudi Arabia in 2012, has caused a total of 2519
laboratory-confirmed cases including 866 associated deaths with a fatality rate of nearly
34% at the end of January 2020.<sup><xref ref-type="bibr" rid="ref25">25</xref>,<xref ref-type="bibr" rid="ref26">26</xref></sup> The lack of effective treatment for coronavirus infections poses a
great challenge to clinical management and highlights the urgent need for new drug
discovery. Wu et al. found that niclosamide was able to inhibit SARS-CoV replication and
totally abolished viral antigen synthesis at a concentration of 1.56 μM after
screening a small marketed drug library.<sup><xref ref-type="bibr" rid="ref27">27</xref></sup> Niclosamide suppressed the
cytopathic effect (CPE) of SARS-CoV at a concentration of as low as 1 μM and
inhibited SARS-CoV replication with an EC<sub>50</sub> value of less than 0.1 μM in
Vero E6 cells.<sup><xref ref-type="bibr" rid="ref28">28</xref></sup> SARS-CoV 3CL protease plays an important role in
replicase polyprotein processing and serves as a key target for anti-SARS drug
discovery.<sup><xref ref-type="bibr" rid="ref29">29</xref>−<xref ref-type="bibr" rid="ref31">31</xref></sup> A series of
2-chloro-4-nitroanilide derivatives was discovered as potent inhibitors against SARS-CoV
3CL protease. Interestingly, niclosamide showed no obvious inhibitory activity against
SARS-CoV 3CL protease up to 50 μM, and mechanistically, it may exert its anti-SARS
activity via other modes of action.<sup><xref ref-type="bibr" rid="ref32">32</xref></sup></p><p>Gassen et al. revealed that E3 ligase S-phase kinase-associated protein 2 (SKP2) executes
lysine-48-linked polyubiquitination of Benclin 1 (BECN1), resulting in its proteasomal
degradation. SKP2 inhibition increases the BENC1 level, enhances autophagy, and
efficiently reduces MERS-CoV replication.<sup><xref ref-type="bibr" rid="ref33">33</xref></sup> Niclosamide was reported to
inhibit MERS-CoV replication by up to 1000-fold at 48 h p.i. at a concentration of 10
μM, while it enhanced the BENC1 level and ATG14 oligomerization, increased the
number of autolysosomes by >2-fold, and affected the autophagic flux in the
MERS-CoV-infected cells.<sup><xref ref-type="bibr" rid="ref33">33</xref></sup> Since niclosamide is a multifunctional drug,
we cannot exclude the possibility that it exerts its anti-MERS activity by regulating
other targets besides SKP2 inhibition.</p></sec><sec id="sec2.2"><title>Niclosamide and Flavivirus</title><p>Flavivirus, a genus of viruses in the family <italic>Flaviviridae</italic>, includes the
Zika virus (ZIKV), dengue virus four serotypes (DENV 1–4), West Nile virus (WNV),
yellow fever virus (YFV), and Japanese encephalitis virus (JEV). Many of these viruses are
significant human pathogens. Among these viruses, ZIKV is a mosquito-borne flavivirus that
is transmitted primarily by <italic>Aedes</italic> mosquitoes. ZIKV infection can cause
infants to be born with microcephaly and can trigger neurologic conditions in adults such
as Guillain–Barré syndrome, neuropathy, and myelitis.<sup><xref ref-type="bibr" rid="ref34">34</xref>−<xref ref-type="bibr" rid="ref38">38</xref></sup> Outbreaks of ZIKV infection have been recorded several
times (2015 in Brazil, the latest one), and the World Health Organization (WHO) declared
ZIKV to be a global public health emergency. Xu et al. used caspase-3 activity as the
primary screening assay and discovered niclosamide as a potent inhibitor of ZIKV
infection, displaying an IC<sub>50</sub> value of 0.37 μM against the intracellular
ZIKV RNA level.<sup><xref ref-type="bibr" rid="ref22">22</xref></sup> The time-of-addition studies indicated that
niclosamide inhibits ZIKV infection at a postentry stage, probably in a viral RNA
replication step. Our research team also identified niclosamide as a potent anti-ZIKV
inhibitor through an independent quantitative high-throughput screening (qHTS) campaign
and found that niclosamide directly inhibits flavivirus NS2B-NS3 interactions.<sup><xref ref-type="bibr" rid="ref14">14</xref></sup> Protease complex NS2B-NS3 is essential for flaviviral polyprotein
processing.<sup><xref ref-type="bibr" rid="ref39">39</xref>−<xref ref-type="bibr" rid="ref41">41</xref></sup> Our team also found that
niclosamide is a broad-spectrum inhibitor against other flaviviruses including DENV-2,
WNV, JEV, and YFV, with potencies similar to that for ZIKV.<sup><xref ref-type="bibr" rid="ref14">14</xref></sup></p><p>In addition, Fang et al. developed a CPE-based HTS assay to screen 1280 pharmacologically
active compounds and identified niclosamide as a potent JEV inhibitor with micromolar
potency.<sup><xref ref-type="bibr" rid="ref42">42</xref></sup> The time-of-addition studies showed that niclosamide
inhibits JEV at the stage of replication.</p></sec><sec id="sec2.3"><title>Niclosamide and Hepatitis C Virus</title><p>Hepatitis C virus (HCV) is an enveloped positive-sense single-strand RNA virus of the
family <italic>Flaviviridae</italic> which is transmitted mainly through blood infection.
HCV can cause both acute and chronic hepatitis, and hepatitis C is a major cause of liver
cancer. It was estimated that about 71 million people have chronic HCV infections
worldwide.<sup><xref ref-type="bibr" rid="ref43">43</xref></sup> At present, there is no effective vaccine against
hepatitis C, although clinically approved therapeutics are available. Niclosamide was
reported to show very promising activity against HCV replication with an EC<sub>50</sub>value of 0.16 μM.<sup><xref ref-type="bibr" rid="ref44">44</xref></sup> It likely inhibits HCV replication via
modulation of the host cell process similar to that of its derivatives nitazoxanide and
tizoxanide.<sup><xref ref-type="bibr" rid="ref45">45</xref>−<xref ref-type="bibr" rid="ref47">47</xref></sup> However, chronic HCV
infection requires long-term (several months) antiviral treatment, which may make a
host-targeted approach less attractive.</p></sec><sec id="sec2.4"><title>Niclosamide and Ebola Virus</title><p>Ebola virus (EBOV) is an enveloped negative-sense single-stranded RNA virus that belongs
to the genus <italic>Ebolavirus</italic> of the family <italic>Filoviridae</italic>. EBOV
is introduced into humans from wild animals and spreads in the human population through
person-to-person transmission. Ebola virus disease (EVD), known as Ebola hemorrhagic
fever, has a high fatality rate, ranging from 25 to 90% in past outbreaks. Through a
systematic screen of FDA-approved drugs, niclosamide was identified as one of the most
potent EBOV inhibitors with an EC<sub>50</sub> value of 1.5 μM, although its
<italic>in vivo</italic> efficacy has not yet been evaluated in animal models.<sup><xref ref-type="bibr" rid="ref48">48</xref></sup></p></sec><sec id="sec2.5"><title>Niclosamide and Human Rhinovirus</title><p>Human rhinoviruses (HRVs) are nonenveloped, positive-sense single-stranded RNA viruses
that belong to the genus <italic>Enterovirus</italic> of the family
<italic>Picornaviridae</italic>. There are more than 100 different HRV strains
classified into three species (HRV A–C). HRVs are widespread among humans and the
primary cause of the common cold, posing serious health risks for patients with asthma,
chronic pulmonary disease, and severe bronchiolitis in infants and children.<sup><xref ref-type="bibr" rid="ref49">49</xref></sup> Niclosamide is a weak lipophilic acid and was reported to inhibit
pH-dependent HRV infection with low micromolar IC<sub>50</sub> values; it suppresses HRV
entry by blocking the acidification of the endolysosomal compartments, acting as a proton
carrier.<sup><xref ref-type="bibr" rid="ref50">50</xref></sup></p></sec><sec id="sec2.6"><title>Niclosamide and Chikungunya Virus</title><p>Chikungunya virus (CHIKV) is a positive-sense single-stranded RNA virus belonging to the
genus <italic>Alphavirus</italic> of the family <italic>Togaviridae</italic>. CHIKV causes
fever and joint pain, is transmitted by infected female mosquitoes, and is cataloged as a
risk group-3 pathogen. Currently, there is no effective antiviral therapy approved for
Chikungunya. Niclosamide was discovered as a potent anti-CHIKV inhibitor with a low
micromolar EC<sub>50</sub> value; it not only affects CHIKV entry via blocking
low-pH-dependent virus fusion but also inhibits the cell-to-cell transmission of CHIKV
infection.<sup><xref ref-type="bibr" rid="ref51">51</xref></sup></p></sec><sec id="sec2.7"><title>Niclosamide and Human Adenovirus</title><p>Human adenoviruses (HAdVs) are nonenveloped double-stranded DNA viruses with icosahedral
capsids. HAdVs comprise more than 70 different serotypes classified into seven species
(HAdV A–G). HAdV infections can cause severe and often life-threatening diseases in
immunosuppressed patients. Currently, no specific antiviral therapy is available to treat
these infections. Three salicylanilide anthelmintic drugs including niclosamide were
screened out as potent anti-HAdV inhibitors. Niclosamide showed very promising anti-HAdV
activity with an EC<sub>50</sub> value of 0.6 μM in the plaque assay. Subsequent
mechanistic studies indicated that niclosamide inhibits the transport of the HAdV particle
from the endosome to the nuclear envelop.<sup><xref ref-type="bibr" rid="ref52">52</xref></sup></p></sec><sec id="sec2.8"><title>Niclosamide and Epstein–Barr Virus</title><p>Epstein–Barr virus (EBV), also known as human herpesvirus 4, has a toroid-shaped
protein core containing a linear double-stranded DNA genome of 184 kb in size which is a
member of the gamma subfamily of herpes viruses. EBV is widely spread in humans and
infects over 95% of humans in the first decades of their life, resulting in a
lymphoproliferative disorder known as infectious mononucleosis. EBV infection was also
found to be associated with the development of several types of cancer such as
Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma.<sup><xref ref-type="bibr" rid="ref53">53</xref></sup> Huang et al. demonstrated that niclosamide inhibits EBV lytic replication
in lymphoma cells and epithelial cells and causes irreversible cell cycle arrest in lytic
EBV-infected cells via disrupting mTOR activation, offering the potential to treat acute
EBV-associated infectious diseases.<sup><xref ref-type="bibr" rid="ref54">54</xref></sup></p></sec></sec><sec id="sec3"><title>Conclusions and Future Directions</title><p>Niclosamide has traditionally been used to treat tapeworm infections for many years, and it
is inexpensive and well tolerated <italic>in vivo</italic> with an extremely high acute oral
LD<sub>50</sub> value of >5000 mg/kg in rats (niclosamide ethanolamine salt).<sup><xref ref-type="bibr" rid="ref10">10</xref></sup> In human medicines, single oral doses of 0.5, 1, and 2 g of niclosamide are
recommended for children under 2 years, children between 2 and 6 years, and children older
than 6 years and adults, respectively, to treat infections with <italic>Taenia
solium</italic>, <italic>T. saginata</italic>, and <italic>Diphyllobothrium
latum</italic>.<sup><xref ref-type="bibr" rid="ref10">10</xref></sup> Human infections with rat tapeworm
<italic>Hymenolepis diminuta</italic> were eliminated by 5–7 daily doses of 2 g of
niclosamide each, while the treatment of <italic>Hymenolepis nana</italic> infection
requires one or several 5–7 day courses of niclosamide treatment. One 7 day course
regimen for adults is 2 g of niclosamide on day 1 followed by 1 g daily for 6
days.<sup><xref ref-type="bibr" rid="ref10">10</xref>,<xref ref-type="bibr" rid="ref55">55</xref></sup> When
treating human volunteers each with a single oral dose of 2000 mg of niclosamide, the
maximum serum concentration of niclosamide was equivalent to 0.25–6.0 μg/mL
(0.76–18.3 μM). The wide concentration range was caused by the intraindividual
absorption differences. Niclosamide is only partially absorbed from the intestinal tract,
and the absorbed part is rapidly eliminated by the kidneys with no cumulative toxic effects
in human.<sup><xref ref-type="bibr" rid="ref10">10</xref></sup> Through a series of drug repurposing screening campaigns,
niclosamide was found to be effective against a variety of human conditions such as cancer
and viral infections. Currently, there are four ongoing human clinical trials of niclosamide
in ulcerative colitis, prostate carcinoma, and colorectal cancer in the ClinicalTrails.gov
clinical trials registry.<sup><xref ref-type="bibr" rid="ref56">56</xref></sup> Of note, niclosamide has several weaknesses
such as unneglectable cytotoxicity and limited aqueous solubility as well as relatively low
absorption and oral bioavailability (<italic>F</italic> = 10%), which may hamper its
extensive clinical development as an antiviral agent.<sup><xref ref-type="bibr" rid="ref57">57</xref></sup> Our group has
made substantial efforts in medicinal chemistry based on niclosamide as a lead compound and
discovered a series of <italic>O</italic>-alkylamino-tethered derivatives as potent and
orally bioavailable anticancer agents with improved aqueous solubility<sup><xref ref-type="bibr" rid="ref16">16</xref></sup>and diversified salicylamide derivatives as potent anti-HAdV inhibitors with increased
potency (submicromolar IC<sub>50</sub>s) and significantly decreased cytotoxicity likely by
targeting different steps in the HAdV life cycle.<sup><xref ref-type="bibr" rid="ref58">58</xref></sup> The ester derivative
prodrug of niclosamide was also reported to increase its systemic drug exposure and extend
the duration of exposure.<sup><xref ref-type="bibr" rid="ref59">59</xref></sup> The development of nanobased formulations is
another useful strategy for improving the pharmacological and pharmacokinetic properties of
niclosamide and maximizing its therapeutic potential for clinical
applications.<sup><xref ref-type="bibr" rid="ref60">60</xref>−<xref ref-type="bibr" rid="ref62">62</xref></sup></p><p>The outbreak of COVID-19 has been declared to be a public health emergency of international
concern by the WHO, and the development of effective therapies for fast-spreading fatal
COVID-19 is in an urgent need. 3CL protease is a key enzyme that is responsible for
proteolytic processing and is indispensable for viral replication and the infection
process.<sup><xref ref-type="bibr" rid="ref6">6</xref></sup> Recently, the high-resolution crystal structure of SARS-CoV-2
3CL protease has been solved by Zihe Rao and Haitao Yang (PDB ID: 6LU7, <xref rid="fig2" ref-type="fig">Figure <xref rid="fig2" ref-type="fig">2</xref></xref>), and this may significantly facilitate the discovery of potent
small-molecule inhibitors of COVID-19 by targeting SARS-CoV-2 3CL protease via
high-throughput virtual screening of compound libraries or existing drug libraries for drug
repurposing. In addition, Wrapp et al. have determined a cryo-EM structure of the SARS-CoV-2
spike (S) glycoprotein trimer in the prefusion conformation that will also facilitate
vaccine development and the discovery of antiviral therapeutics for COVID-19.<sup><xref ref-type="bibr" rid="ref63">63</xref></sup> Although these crystal structures may provide new insights and helpful
information for future drug discovery, extensive efforts are needed to identify effective
binding pockets for small molecules and validate the drug targets.</p><fig id="fig2" position="float"><label>Figure 2</label><caption><p>Crystal structure of SARS-CoV-2 (2019-nCoV) 3CL protease (PDB ID: 6LU7) recently solved by the team of Zihe
Rao and Haitao Yang at ShanghaiTech University, China. The detailed high-resolution
crystal structural analysis of the viral main proteinase (Mpro) of SARS-CoV-2 may
facilitate the <italic>in silico</italic> screening of existing drugs for drug
repurposing or the identification of novel hits from compound libraries by targeting
Mpro, which is considered to be a beneficial drug target regulating the activities of
the virus replication complex.</p></caption><graphic xlink:href="id0c00052_0002" id="gr2" position="float"></graphic></fig><p>It is reported that some existing drugs or drug candidates such as remdesivir, an
RNA-dependent RNA polymerase (RdRp) inhibitor, and lopinavir/ritonavir (protease inhibitors)
against Ebola or HIV may be repurposed through fast-track human clinical trials as effective
therapies to combat deadly COVID-19 and save hundreds of patient lives.<sup><xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref64">64</xref>,<xref ref-type="bibr" rid="ref65">65</xref></sup> Very recently,
through screening the existing antiviral drugs, three broad antiviral agents (nitazoxanide,
remdesivir, and chloroquine) were found to inhibit SARS-CoV-2 at low micromolar
concentrations in Vero E6 cells with EC<sub>50</sub> values of 2.12, 0.77, and 1.13
μM, respectively.<sup><xref ref-type="bibr" rid="ref66">66</xref></sup> Nitazoxanide is a prodrug of tizoxanide, which
shares considerable structural similarity with niclosamide as a salicylamide
derivative.<sup><xref ref-type="bibr" rid="ref47">47</xref></sup> Notably, niclosamide displays promising inhibitory
activity against SARS-CoV replication with an EC<sub>50</sub> value of less than 0.1
μM in Vero E6 cells and inhibits MERS-CoV replication by up to 1000-fold at 48 h p.i.
at a concentration of 10 μM in Vero B4 cells.<sup><xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref33">33</xref></sup> SARS-CoV-2 belongs to the genus
<italic>Betacoronavirus</italic>, the same as SARS-CoV and MERS-CoV, sharing 79.5%
sequence identify to that of SARS-CoV.<sup><xref ref-type="bibr" rid="ref67">67</xref></sup> These findings, together with
its broad antiviral properties, indicate that niclosamide, an inexpensive and well-tolerated
old drug, may be repurposed with therapeutic potential applications to combat COVID-19. We
envision that once its anti-SARS-CoV-2 activity is validated in animal models or human
clinical trials, niclosamide and its optimized analogues may be developed as effective
antiviral therapeutics with the potential to benefit numerous infected patients in this
outbreak of COVID-19.</p></sec></body><back><notes notes-type="COI-statement" id="notes-1"><p>The authors declare no competing financial interest.</p></notes><ack><title>Acknowledgments</title><p>This work was supported by grants R01 AI131669 and R21 AI134568 from the National Institute
of Allergy and Infectious Diseases (NIAID), the National Institutes of Health, John D.
Stobo, the M. D. Distinguished Chair Endowment Fund, and the John Sealy Memorial Endowment
Fund at UTMB. P.-Y.S. was supported by NIH grants AI142759, AI127744, and AI136126, and
awards from the Kleberg Foundation, John S. Dunn Foundation, Amon G. Carter Foundation,
Gilson Longenbaugh Foundation, and Summerfield Robert Foundation. We thank Ms. Xiuna Yang in
Prof. Zihe Rao’s laboratory for her courtesy in sharing the PDB file of SARS-CoV-2
(2019-nCoV) 3CL protease (PDB ID: 6LU7).</p></ack><glossary id="dl1"><def-list><title>Abbreviations Used</title><def-item><term>WHO</term><def><p>World Health Organization</p></def></def-item><def-item><term>COVID-19</term><def><p>coronavirus disease 2019</p></def></def-item><def-item><term>2019-nCoV</term><def><p>the 2019 novel coronavirus</p></def></def-item><def-item><term>MERS-CoV</term><def><p>Middle East respiratory syndrome coronavirus</p></def></def-item><def-item><term>SARS-CoV</term><def><p>severe acute respiratory syndrome coronavirus</p></def></def-item><def-item><term>HCV</term><def><p>hepatitis C virus</p></def></def-item><def-item><term>DENV</term><def><p>dengue virus</p></def></def-item><def-item><term>ZIKV</term><def><p>Zika virus</p></def></def-item><def-item><term>JEV</term><def><p>Japanese encephalitis virus</p></def></def-item><def-item><term>WNV</term><def><p>West Nile virus</p></def></def-item><def-item><term>YFV</term><def><p>yellow fever virus</p></def></def-item><def-item><term>EBOV</term><def><p>Ebola virus</p></def></def-item><def-item><term>HRV</term><def><p>human rhinovirus</p></def></def-item><def-item><term>CHIKV</term><def><p>Chikungunya virus</p></def></def-item><def-item><term>HAdV</term><def><p>human adenovirus</p></def></def-item><def-item><term>EBV</term><def><p>Epstein–Barr virus (EBV)</p></def></def-item><def-item><term>SKP2</term><def><p>S-phase kinase-associated protein 2</p></def></def-item><def-item><term>BECN1</term><def><p>Benclin 1</p></def></def-item><def-item><term>RdRp</term><def><p>RNA-dependent RNA polymerase</p></def></def-item><def-item><term>CPE</term><def><p>cytopathic effect</p></def></def-item><def-item><term>qHTS</term><def><p>quantitative high-throughput screening (qHTS)</p></def></def-item><def-item><term>EC<sub>50</sub></term><def><p>half maximal effective concentration</p></def></def-item><def-item><term>IC<sub>50</sub></term><def><p>half maximal inhibitory concentration</p></def></def-item><def-item><term>LD<sub>50</sub></term><def><p>lethal dose, 50%</p></def></def-item></def-list></glossary><ref-list><title>References</title><ref id="ref1"><mixed-citation publication-type="journal" id="cit1"><name><surname>Huang</surname><given-names>C.</given-names></name>; <name><surname>Wang</surname><given-names>Y.</given-names></name>; <name><surname>Li</surname><given-names>X.</given-names></name>; <name><surname>Ren</surname><given-names>L.</given-names></name>; <name><surname>Zhao</surname><given-names>J.</given-names></name>; <name><surname>Hu</surname><given-names>Y.</given-names></name>; <name><surname>Zhang</surname><given-names>L.</given-names></name>; <name><surname>Fan</surname><given-names>G.</given-names></name>; <name><surname>Xu</surname><given-names>J.</given-names></name>; <name><surname>Gu</surname><given-names>X.</given-names></name>; <name><surname>Cheng</surname><given-names>Z.</given-names></name>; <name><surname>Yu</surname><given-names>T.</given-names></name>; <name><surname>Xia</surname><given-names>J.</given-names></name>; <name><surname>Wei</surname><given-names>Y.</given-names></name>; <name><surname>Wu</surname><given-names>W.</given-names></name>; <name><surname>Xie</surname><given-names>X.</given-names></name>; <name><surname>Yin</surname><given-names>W.</given-names></name>; <name><surname>Li</surname><given-names>H.</given-names></name>; <name><surname>Liu</surname><given-names>M.</given-names></name>; <name><surname>Xiao</surname><given-names>Y.</given-names></name>; <name><surname>Gao</surname><given-names>H.</given-names></name>; <name><surname>Guo</surname><given-names>L.</given-names></name>; <name><surname>Xie</surname><given-names>J.</given-names></name>; <name><surname>Wang</surname><given-names>G.</given-names></name>; <name><surname>Jiang</surname><given-names>R.</given-names></name>; <name><surname>Gao</surname><given-names>Z.</given-names></name>; <name><surname>Jin</surname><given-names>Q.</given-names></name>; <name><surname>Wang</surname><given-names>J.</given-names></name>; <name><surname>Cao</surname><given-names>B.</given-names></name> (<year>2020</year>) <article-title>Clinical features of patients infected with 2019 novel coronavirus in
Wuhan, China</article-title>. <source>Lancet</source><volume>395</volume>, <fpage>497</fpage>–<lpage>506</lpage>. <pub-id pub-id-type="doi">10.1016/S0140-6736(20)30183-5</pub-id>.<pub-id pub-id-type="pmid">31986264</pub-id></mixed-citation></ref><ref id="ref2"><mixed-citation publication-type="book" id="cit2"><person-group person-group-type="allauthors"><name><surname>Fehr</surname><given-names>A. R.</given-names></name>, and
<name><surname>Perlman</surname><given-names>S.</given-names></name></person-group><article-title>Coronaviruses: An Overview of Their Replication and
Pathogenesis</article-title>. In <source>Coronaviruses: Methods and Protocols</source>;
<person-group person-group-type="editor"><name><surname>Maier</surname><given-names>H.
J.</given-names></name>, <name><surname>Bickerton</surname><given-names>E.</given-names></name>, and <name><surname>Britton</surname><given-names>P.</given-names></name></person-group>, Eds.;
<publisher-name>Springer</publisher-name>: <publisher-loc>New York</publisher-loc>,
<year>2015</year>; pp <fpage>1</fpage>–<lpage>23</lpage>.</mixed-citation></ref><ref id="ref3"><mixed-citation publication-type="journal" id="cit3"><name><surname>Hui</surname><given-names>D. S.</given-names></name>; <name><surname>I Azhar</surname><given-names>E.</given-names></name>; <name><surname>Madani</surname><given-names>T. A.</given-names></name>; <name><surname>Ntoumi</surname><given-names>F.</given-names></name>; <name><surname>Kock</surname><given-names>R.</given-names></name>; <name><surname>Dar</surname><given-names>O.</given-names></name>; <name><surname>Ippolito</surname><given-names>G.</given-names></name>; <name><surname>McHugh</surname><given-names>T. D.</given-names></name>; <name><surname>Memish</surname><given-names>Z. A.</given-names></name>; <name><surname>Drosten</surname><given-names>C.</given-names></name>; <name><surname>Zumla</surname><given-names>A.</given-names></name>; <name><surname>Petersen</surname><given-names>E.</given-names></name> (<year>2020</year>) <article-title>The continuing 2019-nCoV epidemic threat of novel coronaviruses to global
health - The latest 2019 novel coronavirus outbreak in Wuhan, China</article-title>. <source>Int. J. Infect. Dis.</source><volume>91</volume>, <fpage>264</fpage>–<lpage>266</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijid.2020.01.009</pub-id>.<pub-id pub-id-type="pmid">31953166</pub-id></mixed-citation></ref><ref id="ref4"><mixed-citation publication-type="journal" id="cit4"><name><surname>Chan</surname><given-names>J. F.-W.</given-names></name>; <name><surname>Yuan</surname><given-names>S.</given-names></name>; <name><surname>Kok</surname><given-names>K.-H.</given-names></name>; <name><surname>To</surname><given-names>K. K.-W.</given-names></name>; <name><surname>Chu</surname><given-names>H.</given-names></name>; <name><surname>Yang</surname><given-names>J.</given-names></name>; <name><surname>Xing</surname><given-names>F.</given-names></name>; <name><surname>Liu</surname><given-names>J.</given-names></name>; <name><surname>Yip</surname><given-names>C. C.-Y.</given-names></name>; <name><surname>Poon</surname><given-names>R. W.-S.</given-names></name>; <name><surname>Tsoi</surname><given-names>H.-W.</given-names></name>; <name><surname>Lo</surname><given-names>S. K.-F.</given-names></name>; <name><surname>Chan</surname><given-names>K.-H.</given-names></name>; <name><surname>Poon</surname><given-names>V. K.-M.</given-names></name>; <name><surname>Chan</surname><given-names>W.-M.</given-names></name>; <name><surname>Ip</surname><given-names>J. D.</given-names></name>; <name><surname>Cai</surname><given-names>J.-P.</given-names></name>; <name><surname>Cheng</surname><given-names>V. C.-C.</given-names></name>; <name><surname>Chen</surname><given-names>H.</given-names></name>; <name><surname>Hui</surname><given-names>C. K.-M.</given-names></name>; <name><surname>Yuen</surname><given-names>K.-Y.</given-names></name> (<year>2020</year>) <article-title>A familial cluster of pneumonia associated with the 2019 novel coronavirus
indicating person-to-person transmission: a study of a family cluster</article-title>. <source>Lancet</source><volume>395</volume>, <fpage>514</fpage>–<lpage>523</lpage>. <pub-id pub-id-type="doi">10.1016/S0140-6736(20)30154-9</pub-id>.<pub-id pub-id-type="pmid">31986261</pub-id></mixed-citation></ref><ref id="ref5"><mixed-citation publication-type="weblink" id="cit5"><person-group><collab>World Health
Organization</collab></person-group>. Coronavirus disease (COVID-2019) situation
reports. Situation reports - 45. <uri xlink:href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/">https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/</uri>(accessed Feb 27, 2020).</mixed-citation></ref><ref id="ref6"><mixed-citation publication-type="journal" id="cit6"><name><surname>Zumla</surname><given-names>A.</given-names></name>; <name><surname>Chan</surname><given-names>J. F. W.</given-names></name>; <name><surname>Azhar</surname><given-names>E. I.</given-names></name>; <name><surname>Hui</surname><given-names>D. S. C.</given-names></name>; <name><surname>Yuen</surname><given-names>K.-Y.</given-names></name> (<year>2016</year>) <article-title>Coronaviruses - drug discovery and therapeutic options</article-title>. <source>Nat. Rev. Drug Discovery</source><volume>15</volume>, <fpage>327</fpage>–<lpage>347</lpage>. <pub-id pub-id-type="doi">10.1038/nrd.2015.37</pub-id>.<pub-id pub-id-type="pmid">26868298</pub-id></mixed-citation></ref><ref id="ref7"><mixed-citation publication-type="journal" id="cit7"><name><surname>Holshue</surname><given-names>M. L.</given-names></name>; <name><surname>DeBolt</surname><given-names>C.</given-names></name>; <name><surname>Lindquist</surname><given-names>S.</given-names></name>; <name><surname>Lofy</surname><given-names>K. H.</given-names></name>; <name><surname>Wiesman</surname><given-names>J.</given-names></name>; <name><surname>Bruce</surname><given-names>H.</given-names></name>; <name><surname>Spitters</surname><given-names>C.</given-names></name>; <name><surname>Ericson</surname><given-names>K.</given-names></name>; <name><surname>Wilkerson</surname><given-names>S.</given-names></name>; <name><surname>Tural</surname><given-names>A.</given-names></name>; <name><surname>Diaz</surname><given-names>G.</given-names></name>; <name><surname>Cohn</surname><given-names>A.</given-names></name>; <name><surname>Fox</surname><given-names>L.</given-names></name>; <name><surname>Patel</surname><given-names>A.</given-names></name>; <name><surname>Gerber</surname><given-names>S. I.</given-names></name>; <name><surname>Kim</surname><given-names>L.</given-names></name>; <name><surname>Tong</surname><given-names>S.</given-names></name>; <name><surname>Lu</surname><given-names>X.</given-names></name>; <name><surname>Lindstrom</surname><given-names>S.</given-names></name>; <name><surname>Pallansch</surname><given-names>M. A.</given-names></name>; <name><surname>Weldon</surname><given-names>W. C.</given-names></name>; <name><surname>Biggs</surname><given-names>H. M.</given-names></name>; <name><surname>Uyeki</surname><given-names>T. M.</given-names></name>; <name><surname>Pillai</surname><given-names>S. K.</given-names></name> (<year>2020</year>) <article-title>First case of 2019 novel coronavirus in the United States</article-title>. <source>N. Engl. J. Med.</source><pub-id pub-id-type="doi">10.1056/NEJMoa2001191</pub-id>.</mixed-citation></ref><ref id="ref8"><mixed-citation publication-type="journal" id="cit8"><name><surname>Ashburn</surname><given-names>T. T.</given-names></name>; <name><surname>Thor</surname><given-names>K. B.</given-names></name> (<year>2004</year>) <article-title>Drug repositioning: identifying and developing new uses for existing
drugs</article-title>. <source>Nat. Rev. Drug Discovery</source><volume>3</volume>, <fpage>673</fpage>–<lpage>683</lpage>. <pub-id pub-id-type="doi">10.1038/nrd1468</pub-id>.<pub-id pub-id-type="pmid">15286734</pub-id></mixed-citation></ref><ref id="ref9"><mixed-citation publication-type="journal" id="cit9"><name><surname>Pushpakom</surname><given-names>S.</given-names></name>; <name><surname>Iorio</surname><given-names>F.</given-names></name>; <name><surname>Eyers</surname><given-names>P. A.</given-names></name>; <name><surname>Escott</surname><given-names>K. J.</given-names></name>; <name><surname>Hopper</surname><given-names>S.</given-names></name>; <name><surname>Wells</surname><given-names>A.</given-names></name>; <name><surname>Doig</surname><given-names>A.</given-names></name>; <name><surname>Guilliams</surname><given-names>T.</given-names></name>; <name><surname>Latimer</surname><given-names>J.</given-names></name>; <name><surname>McNamee</surname><given-names>C.</given-names></name>; <name><surname>Norris</surname><given-names>A.</given-names></name>; <name><surname>Sanseau</surname><given-names>P.</given-names></name>; <name><surname>Cavalla</surname><given-names>D.</given-names></name>; <name><surname>Pirmohamed</surname><given-names>M.</given-names></name> (<year>2019</year>) <article-title>Drug repurposing: progress, challenges and recommendations</article-title>. <source>Nat. Rev. Drug Discovery</source><volume>18</volume>, <fpage>41</fpage>–<lpage>58</lpage>. <pub-id pub-id-type="doi">10.1038/nrd.2018.168</pub-id>.<pub-id pub-id-type="pmid">30310233</pub-id></mixed-citation></ref><ref id="ref10"><mixed-citation publication-type="journal" id="cit10"><name><surname>Andrews</surname><given-names>P.</given-names></name>; <name><surname>Thyssen</surname><given-names>J.</given-names></name>; <name><surname>Lorke</surname><given-names>D.</given-names></name> (<year>1982</year>) <article-title>The biology and toxicology of molluscicides, bayluscide</article-title>. <source>Pharmacol. Ther.</source><volume>19</volume>, <fpage>245</fpage>–<lpage>295</lpage>. <pub-id pub-id-type="doi">10.1016/0163-7258(82)90064-X</pub-id>.<pub-id pub-id-type="pmid">6763710</pub-id></mixed-citation></ref><ref id="ref11"><mixed-citation publication-type="undeclared" id="cit11"><person-group><collab>World Health
Organization</collab></person-group>. <italic>World Health Organization Model List of
Essential Medicines</italic>, <italic>21st List</italic>, <year>2019</year>.</mixed-citation></ref><ref id="ref12"><mixed-citation publication-type="journal" id="cit12"><name><surname>Weinbach</surname><given-names>E. C.</given-names></name>; <name><surname>Garbus</surname><given-names>J.</given-names></name> (<year>1969</year>) <article-title>Mechanism of action of reagents that uncouple oxidative
phosphorylation</article-title>. <source>Nature</source><volume>221</volume>, <fpage>1016</fpage>–<lpage>1018</lpage>. <pub-id pub-id-type="doi">10.1038/2211016a0</pub-id>.<pub-id pub-id-type="pmid">4180173</pub-id></mixed-citation></ref><ref id="ref13"><mixed-citation publication-type="journal" id="cit13"><name><surname>Li</surname><given-names>Y.</given-names></name>; <name><surname>Li</surname><given-names>P.-K.</given-names></name>; <name><surname>Roberts</surname><given-names>M. J.</given-names></name>; <name><surname>Arend</surname><given-names>R. C.</given-names></name>; <name><surname>Samant</surname><given-names>R. S.</given-names></name>; <name><surname>Buchsbaum</surname><given-names>D. J.</given-names></name> (<year>2014</year>) <article-title>Multi-targeted therapy of cancer by niclosamide: A new application for an
old drug</article-title>. <source>Cancer Lett.</source><volume>349</volume>, <fpage>8</fpage>–<lpage>14</lpage>. <pub-id pub-id-type="doi">10.1016/j.canlet.2014.04.003</pub-id>.<pub-id pub-id-type="pmid">24732808</pub-id></mixed-citation></ref><ref id="ref14"><mixed-citation publication-type="journal" id="cit14"><name><surname>Li</surname><given-names>Z.</given-names></name>; <name><surname>Brecher</surname><given-names>M.</given-names></name>; <name><surname>Deng</surname><given-names>Y.-Q.</given-names></name>; <name><surname>Zhang</surname><given-names>J.</given-names></name>; <name><surname>Sakamuru</surname><given-names>S.</given-names></name>; <name><surname>Liu</surname><given-names>B.</given-names></name>; <name><surname>Huang</surname><given-names>R.</given-names></name>; <name><surname>Koetzner</surname><given-names>C. A.</given-names></name>; <name><surname>Allen</surname><given-names>C. A.</given-names></name>; <name><surname>Jones</surname><given-names>S. A.</given-names></name>; <name><surname>Chen</surname><given-names>H.</given-names></name>; <name><surname>Zhang</surname><given-names>N.-N.</given-names></name>; <name><surname>Tian</surname><given-names>M.</given-names></name>; <name><surname>Gao</surname><given-names>F.</given-names></name>; <name><surname>Lin</surname><given-names>Q.</given-names></name>; <name><surname>Banavali</surname><given-names>N.</given-names></name>; <name><surname>Zhou</surname><given-names>J.</given-names></name>; <name><surname>Boles</surname><given-names>N.</given-names></name>; <name><surname>Xia</surname><given-names>M.</given-names></name>; <name><surname>Kramer</surname><given-names>L. D.</given-names></name>; <name><surname>Qin</surname><given-names>C.-F.</given-names></name>; <name><surname>Li</surname><given-names>H.</given-names></name> (<year>2017</year>) <article-title>Existing drugs as broad-spectrum and potent inhibitors for Zika virus by
targeting NS2B-NS3 interaction</article-title>. <source>Cell Res.</source><volume>27</volume>, <fpage>1046</fpage>–<lpage>1064</lpage>. <pub-id pub-id-type="doi">10.1038/cr.2017.88</pub-id>.<pub-id pub-id-type="pmid">28685770</pub-id></mixed-citation></ref><ref id="ref15"><mixed-citation publication-type="journal" id="cit15"><name><surname>Chen</surname><given-names>W.</given-names></name>; <name><surname>Mook</surname><given-names>R. A.</given-names></name>; <name><surname>Premont</surname><given-names>R. T.</given-names></name>; <name><surname>Wang</surname><given-names>J.</given-names></name> (<year>2018</year>) <article-title>Niclosamide: Beyond an antihelminthic drug</article-title>. <source>Cell. Signalling</source><volume>41</volume>, <fpage>89</fpage>–<lpage>96</lpage>. <pub-id pub-id-type="doi">10.1016/j.cellsig.2017.04.001</pub-id>.<pub-id pub-id-type="pmid">28389414</pub-id></mixed-citation></ref><ref id="ref16"><mixed-citation publication-type="journal" id="cit16"><name><surname>Chen</surname><given-names>H.</given-names></name>; <name><surname>Yang</surname><given-names>Z.</given-names></name>; <name><surname>Ding</surname><given-names>C.</given-names></name>; <name><surname>Chu</surname><given-names>L.</given-names></name>; <name><surname>Zhang</surname><given-names>Y.</given-names></name>; <name><surname>Terry</surname><given-names>K.</given-names></name>; <name><surname>Liu</surname><given-names>H.</given-names></name>; <name><surname>Shen</surname><given-names>Q.</given-names></name>; <name><surname>Zhou</surname><given-names>J.</given-names></name> (<year>2013</year>) <article-title>Discovery of O-alkylamino-tethered niclosamide derivatives as potent and
orally bioavailable anticancer agents</article-title>. <source>ACS Med. Chem. Lett.</source><volume>4</volume>, <fpage>180</fpage>–<lpage>185</lpage>. <pub-id pub-id-type="doi">10.1021/ml3003082</pub-id>.<pub-id pub-id-type="pmid">23459613</pub-id></mixed-citation></ref><ref id="ref17"><mixed-citation publication-type="journal" id="cit17"><name><surname>Satoh</surname><given-names>K.</given-names></name>; <name><surname>Zhang</surname><given-names>L.</given-names></name>; <name><surname>Zhang</surname><given-names>Y.</given-names></name>; <name><surname>Chelluri</surname><given-names>R.</given-names></name>; <name><surname>Boufraqech</surname><given-names>M.</given-names></name>; <name><surname>Nilubol</surname><given-names>N.</given-names></name>; <name><surname>Patel</surname><given-names>D.</given-names></name>; <name><surname>Shen</surname><given-names>M.</given-names></name>; <name><surname>Kebebew</surname><given-names>E.</given-names></name> (<year>2016</year>) <article-title>Identification of niclosamide as a novel anticancer agent for
adrenocortical carcinoma</article-title>. <source>Clin. Cancer Res.</source><volume>22</volume>, <fpage>3458</fpage>–<lpage>3466</lpage>. <pub-id pub-id-type="doi">10.1158/1078-0432.CCR-15-2256</pub-id>.<pub-id pub-id-type="pmid">26873959</pub-id></mixed-citation></ref><ref id="ref18"><mixed-citation publication-type="journal" id="cit18"><name><surname>Osada</surname><given-names>T.</given-names></name>; <name><surname>Chen</surname><given-names>M.</given-names></name>; <name><surname>Yang</surname><given-names>X. Y.</given-names></name>; <name><surname>Spasojevic</surname><given-names>I.</given-names></name>; <name><surname>Vandeusen</surname><given-names>J. B.</given-names></name>; <name><surname>Hsu</surname><given-names>D.</given-names></name>; <name><surname>Clary</surname><given-names>B. M.</given-names></name>; <name><surname>Clay</surname><given-names>T. M.</given-names></name>; <name><surname>Chen</surname><given-names>W.</given-names></name>; <name><surname>Morse</surname><given-names>M. A.</given-names></name>; <name><surname>Lyerly</surname><given-names>H. K.</given-names></name> (<year>2011</year>) <article-title>Antihelminth compound niclosamide downregulates Wnt signaling and elicits
antitumor responses in tumors with activating APC mutations</article-title>. <source>Cancer Res.</source><volume>71</volume>, <fpage>4172</fpage>–<lpage>4182</lpage>. <pub-id pub-id-type="doi">10.1158/0008-5472.CAN-10-3978</pub-id>.<pub-id pub-id-type="pmid">21531761</pub-id></mixed-citation></ref><ref id="ref19"><mixed-citation publication-type="journal" id="cit19"><name><surname>Xu</surname><given-names>J.</given-names></name>; <name><surname>Pachón-Ibáñez</surname><given-names>M. E.</given-names></name>; <name><surname>Cebrero-Cangueiro</surname><given-names>T.</given-names></name>; <name><surname>Chen</surname><given-names>H.</given-names></name>; <name><surname>Sánchez-Céspedes</surname><given-names>J.</given-names></name>; <name><surname>Zhou</surname><given-names>J.</given-names></name> (<year>2019</year>) <article-title>Discovery of niclosamide and its O-alkylamino-tethered derivatives as
potent antibacterial agents against carbapenemase-producing and/or colistin resistant
Enterobacteriaceae isolates</article-title>. <source>Bioorg. Med. Chem. Lett.</source><volume>29</volume>, <fpage>1399</fpage>–<lpage>1402</lpage>. <pub-id pub-id-type="doi">10.1016/j.bmcl.2019.03.032</pub-id>.<pub-id pub-id-type="pmid">30954430</pub-id></mixed-citation></ref><ref id="ref20"><mixed-citation publication-type="journal" id="cit20"><name><surname>Fan</surname><given-names>X.</given-names></name>; <name><surname>Xu</surname><given-names>J.</given-names></name>; <name><surname>Files</surname><given-names>M.</given-names></name>; <name><surname>Cirillo</surname><given-names>J. D.</given-names></name>; <name><surname>Endsley</surname><given-names>J. J.</given-names></name>; <name><surname>Zhou</surname><given-names>J.</given-names></name>; <name><surname>Endsley</surname><given-names>M. A.</given-names></name> (<year>2019</year>) <article-title>Dual activity of niclosamide to suppress replication of integrated HIV-1
and Mycobacterium tuberculosis (Beijing)</article-title>. <source>Tuberculosis</source><volume>116</volume>, <fpage>S28</fpage>–<lpage>S33</lpage>. <pub-id pub-id-type="doi">10.1016/j.tube.2019.04.008</pub-id>.</mixed-citation></ref><ref id="ref21"><mixed-citation publication-type="journal" id="cit21"><name><surname>Sun</surname><given-names>Z.</given-names></name>; <name><surname>Zhang</surname><given-names>Y.</given-names></name> (<year>1999</year>) <article-title>Antituberculosis activity of certain antifungal and antihelmintic
drugs</article-title>. <source>Tuber. Lung Dis.</source><volume>79</volume>, <fpage>319</fpage>–<lpage>320</lpage>. <pub-id pub-id-type="doi">10.1054/tuld.1999.0212</pub-id>.<pub-id pub-id-type="pmid">10707260</pub-id></mixed-citation></ref><ref id="ref22"><mixed-citation publication-type="journal" id="cit22"><name><surname>Xu</surname><given-names>M.</given-names></name>; <name><surname>Lee</surname><given-names>E. M.</given-names></name>; <name><surname>Wen</surname><given-names>Z.</given-names></name>; <name><surname>Cheng</surname><given-names>Y.</given-names></name>; <name><surname>Huang</surname><given-names>W.-K.</given-names></name>; <name><surname>Qian</surname><given-names>X.</given-names></name>; <name><surname>Tcw</surname><given-names>J.</given-names></name>; <name><surname>Kouznetsova</surname><given-names>J.</given-names></name>; <name><surname>Ogden</surname><given-names>S. C.</given-names></name>; <name><surname>Hammack</surname><given-names>C.</given-names></name>; <name><surname>Jacob</surname><given-names>F.</given-names></name>; <name><surname>Nguyen</surname><given-names>H. N.</given-names></name>; <name><surname>Itkin</surname><given-names>M.</given-names></name>; <name><surname>Hanna</surname><given-names>C.</given-names></name>; <name><surname>Shinn</surname><given-names>P.</given-names></name>; <name><surname>Allen</surname><given-names>C.</given-names></name>; <name><surname>Michael</surname><given-names>S. G.</given-names></name>; <name><surname>Simeonov</surname><given-names>A.</given-names></name>; <name><surname>Huang</surname><given-names>W.</given-names></name>; <name><surname>Christian</surname><given-names>K. M.</given-names></name>; <name><surname>Goate</surname><given-names>A.</given-names></name>; <name><surname>Brennand</surname><given-names>K. J.</given-names></name>; <name><surname>Huang</surname><given-names>R.</given-names></name>; <name><surname>Xia</surname><given-names>M.</given-names></name>; <name><surname>Ming</surname><given-names>G.-l.</given-names></name>; <name><surname>Zheng</surname><given-names>W.</given-names></name>; <name><surname>Song</surname><given-names>H.</given-names></name>; <name><surname>Tang</surname><given-names>H.</given-names></name> (<year>2016</year>) <article-title>Identification of small-molecule inhibitors of Zika virus infection and
induced neural cell death via a drug repurposing screen</article-title>. <source>Nat. Med.</source><volume>22</volume>, <fpage>1101</fpage>–<lpage>1107</lpage>. <pub-id pub-id-type="doi">10.1038/nm.4184</pub-id>.<pub-id pub-id-type="pmid">27571349</pub-id></mixed-citation></ref><ref id="ref23"><mixed-citation publication-type="journal" id="cit23"><name><surname>Tao</surname><given-names>H.</given-names></name>; <name><surname>Zhang</surname><given-names>Y.</given-names></name>; <name><surname>Zeng</surname><given-names>X.</given-names></name>; <name><surname>Shulman</surname><given-names>G. I.</given-names></name>; <name><surname>Jin</surname><given-names>S.</given-names></name> (<year>2014</year>) <article-title>Niclosamide ethanolamine–induced mild mitochondrial uncoupling
improves diabetic symptoms in mice</article-title>. <source>Nat. Med.</source><volume>20</volume>, <fpage>1263</fpage>–<lpage>1269</lpage>. <pub-id pub-id-type="doi">10.1038/nm.3699</pub-id>.<pub-id pub-id-type="pmid">25282357</pub-id></mixed-citation></ref><ref id="ref24"><mixed-citation publication-type="book" id="cit24"><person-group person-group-type="allauthors"><name><surname>Corman</surname><given-names>V. M.</given-names></name>,
<name><surname>Muth</surname><given-names>D.</given-names></name>,
<name><surname>Niemeyer</surname><given-names>D.</given-names></name>, and
<name><surname>Drosten</surname><given-names>C.</given-names></name></person-group> In
<source>Advances in Virus Research</source>; <person-group person-group-type="editor"><name><surname>Kielian</surname><given-names>M.</given-names></name>,
<name><surname>Mettenleiter</surname><given-names>T. C.</given-names></name>, and
<name><surname>Roossinck</surname><given-names>M.
J.</given-names></name></person-group>, Eds.; <publisher-name>Academic
Press</publisher-name>: <year>2018</year>; Vol. <volume>100</volume>, Chapter 8, pp
<fpage>163</fpage>–<lpage>188</lpage>.</mixed-citation></ref><ref id="ref25"><mixed-citation publication-type="weblink" id="cit25"><person-group><collab>World Health
Organization</collab></person-group>. Summary of probable SARS cases with onset of
illness from 1 November 2002 to 31 July 2003. December 31, 2003. <uri xlink:href="https://www.who.int/csr/sars/country/table2004_04_21/en/">https://www.who.int/csr/sars/country/table2004_04_21/en/</uri> (accessed Feb 26,
2020).</mixed-citation></ref><ref id="ref26"><mixed-citation publication-type="weblink" id="cit26"><person-group><collab>World Health
Organization</collab></person-group>. <article-title>Middle East respiratory syndrome
coronavirus (MERS-CoV)</article-title>. January, <year>2020</year>. <uri xlink:href="https://www.who.int/emergencies/mers-cov/en/">https://www.who.int/emergencies/mers-cov/en/</uri> (acessed Feb 26, 2020).</mixed-citation></ref><ref id="ref27"><mixed-citation publication-type="journal" id="cit27"><name><surname>Wu</surname><given-names>C.-J.</given-names></name>; <name><surname>Jan</surname><given-names>J.-T.</given-names></name>; <name><surname>Chen</surname><given-names>C.-M.</given-names></name>; <name><surname>Hsieh</surname><given-names>H.-P.</given-names></name>; <name><surname>Hwang</surname><given-names>D.-R.</given-names></name>; <name><surname>Liu</surname><given-names>H.-W.</given-names></name>; <name><surname>Liu</surname><given-names>C.-Y.</given-names></name>; <name><surname>Huang</surname><given-names>H.-W.</given-names></name>; <name><surname>Chen</surname><given-names>S.-C.</given-names></name>; <name><surname>Hong</surname><given-names>C.-F.</given-names></name>; <name><surname>Lin</surname><given-names>R.-K.</given-names></name>; <name><surname>Chao</surname><given-names>Y.-S.</given-names></name>; <name><surname>Hsu</surname><given-names>J. T. A.</given-names></name> (<year>2004</year>) <article-title>Inhibition of severe acute respiratory syndrome coronavirus replication by
niclosamide</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>48</volume>, <fpage>2693</fpage>–<lpage>2696</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.48.7.2693-2696.2004</pub-id>.<pub-id pub-id-type="pmid">15215127</pub-id></mixed-citation></ref><ref id="ref28"><mixed-citation publication-type="journal" id="cit28"><name><surname>Wen</surname><given-names>C.-C.</given-names></name>; <name><surname>Kuo</surname><given-names>Y.-H.</given-names></name>; <name><surname>Jan</surname><given-names>J.-T.</given-names></name>; <name><surname>Liang</surname><given-names>P.-H.</given-names></name>; <name><surname>Wang</surname><given-names>S.-Y.</given-names></name>; <name><surname>Liu</surname><given-names>H.-G.</given-names></name>; <name><surname>Lee</surname><given-names>C.-K.</given-names></name>; <name><surname>Chang</surname><given-names>S.-T.</given-names></name>; <name><surname>Kuo</surname><given-names>C.-J.</given-names></name>; <name><surname>Lee</surname><given-names>S.-S.</given-names></name>; <name><surname>Hou</surname><given-names>C.-C.</given-names></name>; <name><surname>Hsiao</surname><given-names>P.-W.</given-names></name>; <name><surname>Chien</surname><given-names>S.-C.</given-names></name>; <name><surname>Shyur</surname><given-names>L.-F.</given-names></name>; <name><surname>Yang</surname><given-names>N.-S.</given-names></name> (<year>2007</year>) <article-title>Specific plant terpenoids and lignoids possess potent antiviral activities
against severe acute respiratory syndrome coronavirus</article-title>. <source>J. Med. Chem.</source><volume>50</volume>, <fpage>4087</fpage>–<lpage>4095</lpage>. <pub-id pub-id-type="doi">10.1021/jm070295s</pub-id>.<pub-id pub-id-type="pmid">17663539</pub-id></mixed-citation></ref><ref id="ref29"><mixed-citation publication-type="journal" id="cit29"><name><surname>Anand</surname><given-names>K.</given-names></name>; <name><surname>Ziebuhr</surname><given-names>J.</given-names></name>; <name><surname>Wadhwani</surname><given-names>P.</given-names></name>; <name><surname>Mesters</surname><given-names>J. R.</given-names></name>; <name><surname>Hilgenfeld</surname><given-names>R.</given-names></name> (<year>2003</year>) <article-title>Coronavirus main proteinase (3CL<sup>pro</sup>) structure: Basis for design
of anti-SARS drugs</article-title>. <source>Science</source><volume>300</volume>, <fpage>1763</fpage>–<lpage>1767</lpage>. <pub-id pub-id-type="doi">10.1126/science.1085658</pub-id>.<pub-id pub-id-type="pmid">12746549</pub-id></mixed-citation></ref><ref id="ref30"><mixed-citation publication-type="journal" id="cit30"><name><surname>Yang</surname><given-names>H.</given-names></name>; <name><surname>Yang</surname><given-names>M.</given-names></name>; <name><surname>Ding</surname><given-names>Y.</given-names></name>; <name><surname>Liu</surname><given-names>Y.</given-names></name>; <name><surname>Lou</surname><given-names>Z.</given-names></name>; <name><surname>Zhou</surname><given-names>Z.</given-names></name>; <name><surname>Sun</surname><given-names>L.</given-names></name>; <name><surname>Mo</surname><given-names>L.</given-names></name>; <name><surname>Ye</surname><given-names>S.</given-names></name>; <name><surname>Pang</surname><given-names>H.</given-names></name>; <name><surname>Gao</surname><given-names>G. F.</given-names></name>; <name><surname>Anand</surname><given-names>K.</given-names></name>; <name><surname>Bartlam</surname><given-names>M.</given-names></name>; <name><surname>Hilgenfeld</surname><given-names>R.</given-names></name>; <name><surname>Rao</surname><given-names>Z.</given-names></name> (<year>2003</year>) <article-title>The crystal structures of severe acute respiratory syndrome virus main
protease and its complex with an inhibitor</article-title>. <source>Proc. Natl. Acad. Sci. U. S. A.</source><volume>100</volume>, <fpage>13190</fpage>–<lpage>13195</lpage>. <pub-id pub-id-type="doi">10.1073/pnas.1835675100</pub-id>.<pub-id pub-id-type="pmid">14585926</pub-id></mixed-citation></ref><ref id="ref31"><mixed-citation publication-type="journal" id="cit31"><name><surname>Chou</surname><given-names>K.-C.</given-names></name>; <name><surname>Wei</surname><given-names>D.-Q.</given-names></name>; <name><surname>Zhong</surname><given-names>W.-Z.</given-names></name> (<year>2003</year>) <article-title>Binding mechanism of coronavirus main proteinase with ligands and its
implication to drug design against SARS</article-title>. <source>Biochem. Biophys. Res. Commun.</source><volume>308</volume>, <fpage>148</fpage>–<lpage>151</lpage>. <pub-id pub-id-type="doi">10.1016/S0006-291X(03)01342-1</pub-id>.<pub-id pub-id-type="pmid">12890493</pub-id></mixed-citation></ref><ref id="ref32"><mixed-citation publication-type="journal" id="cit32"><name><surname>Shie</surname><given-names>J.-J.</given-names></name>; <name><surname>Fang</surname><given-names>J.-M.</given-names></name>; <name><surname>Kuo</surname><given-names>C.-J.</given-names></name>; <name><surname>Kuo</surname><given-names>T.-H.</given-names></name>; <name><surname>Liang</surname><given-names>P.-H.</given-names></name>; <name><surname>Huang</surname><given-names>H.-J.</given-names></name>; <name><surname>Yang</surname><given-names>W.-B.</given-names></name>; <name><surname>Lin</surname><given-names>C.-H.</given-names></name>; <name><surname>Chen</surname><given-names>J.-L.</given-names></name>; <name><surname>Wu</surname><given-names>Y.-T.</given-names></name>; <name><surname>Wong</surname><given-names>C.-H.</given-names></name> (<year>2005</year>) <article-title>Discovery of potent anilide inhibitors against the severe acute respiratory
syndrome 3CL protease</article-title>. <source>J. Med. Chem.</source><volume>48</volume>, <fpage>4469</fpage>–<lpage>4473</lpage>. <pub-id pub-id-type="doi">10.1021/jm050184y</pub-id>.<pub-id pub-id-type="pmid">15974598</pub-id></mixed-citation></ref><ref id="ref33"><mixed-citation publication-type="journal" id="cit33"><name><surname>Gassen</surname><given-names>N. C.</given-names></name>; <name><surname>Niemeyer</surname><given-names>D.</given-names></name>; <name><surname>Muth</surname><given-names>D.</given-names></name>; <name><surname>Corman</surname><given-names>V. M.</given-names></name>; <name><surname>Martinelli</surname><given-names>S.</given-names></name>; <name><surname>Gassen</surname><given-names>A.</given-names></name>; <name><surname>Hafner</surname><given-names>K.</given-names></name>; <name><surname>Papies</surname><given-names>J.</given-names></name>; <name><surname>Mosbauer</surname><given-names>K.</given-names></name>; <name><surname>Zellner</surname><given-names>A.</given-names></name>; <name><surname>Zannas</surname><given-names>A. S.</given-names></name>; <name><surname>Herrmann</surname><given-names>A.</given-names></name>; <name><surname>Holsboer</surname><given-names>F.</given-names></name>; <name><surname>Brack-Werner</surname><given-names>R.</given-names></name>; <name><surname>Boshart</surname><given-names>M.</given-names></name>; <name><surname>Muller-Myhsok</surname><given-names>B.</given-names></name>; <name><surname>Drosten</surname><given-names>C.</given-names></name>; <name><surname>Muller</surname><given-names>M. A.</given-names></name>; <name><surname>Rein</surname><given-names>T.</given-names></name> (<year>2019</year>) <article-title>SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition
reduces MERS-Coronavirus infection</article-title>. <source>Nat. Commun.</source><volume>10</volume>, <fpage>5770</fpage><pub-id pub-id-type="doi">10.1038/s41467-019-13659-4</pub-id>.<pub-id pub-id-type="pmid">31852899</pub-id></mixed-citation></ref><ref id="ref34"><mixed-citation publication-type="journal" id="cit34"><name><surname>Mlakar</surname><given-names>J.</given-names></name>; <name><surname>Korva</surname><given-names>M.</given-names></name>; <name><surname>Tul</surname><given-names>N.</given-names></name>; <name><surname>Popović</surname><given-names>M.</given-names></name>; <name><surname>Poljšak-Prijatelj</surname><given-names>M.</given-names></name>; <name><surname>Mraz</surname><given-names>J.</given-names></name>; <name><surname>Kolenc</surname><given-names>M.</given-names></name>; <name><surname>Resman Rus</surname><given-names>K.</given-names></name>; <name><surname>Vesnaver Vipotnik</surname><given-names>T.</given-names></name>; <name><surname>Fabjan Vodušek</surname><given-names>V.</given-names></name>; <name><surname>Vizjak</surname><given-names>A.</given-names></name>; <name><surname>Pižem</surname><given-names>J.</given-names></name>; <name><surname>Petrovec</surname><given-names>M.</given-names></name>; <name><surname>Avšič Županc</surname><given-names>T.</given-names></name> (<year>2016</year>) <article-title>Zika virus associated with microcephaly</article-title>. <source>N. Engl. J. Med.</source><volume>374</volume>, <fpage>951</fpage>–<lpage>958</lpage>. <pub-id pub-id-type="doi">10.1056/NEJMoa1600651</pub-id>.<pub-id pub-id-type="pmid">26862926</pub-id></mixed-citation></ref><ref id="ref35"><mixed-citation publication-type="journal" id="cit35"><name><surname>Rasmussen</surname><given-names>S. A.</given-names></name>; <name><surname>Jamieson</surname><given-names>D. J.</given-names></name>; <name><surname>Honein</surname><given-names>M. A.</given-names></name>; <name><surname>Petersen</surname><given-names>L. R.</given-names></name> (<year>2016</year>) <article-title>Zika virus and birth defects - reviewing the evidence for
causality</article-title>. <source>N. Engl. J. Med.</source><volume>374</volume>, <fpage>1981</fpage>–<lpage>1987</lpage>. <pub-id pub-id-type="doi">10.1056/NEJMsr1604338</pub-id>.<pub-id pub-id-type="pmid">27074377</pub-id></mixed-citation></ref><ref id="ref36"><mixed-citation publication-type="journal" id="cit36"><name><surname>Petersen</surname><given-names>E.</given-names></name>; <name><surname>Wilson</surname><given-names>M. E.</given-names></name>; <name><surname>Touch</surname><given-names>S.</given-names></name>; <name><surname>McCloskey</surname><given-names>B.</given-names></name>; <name><surname>Mwaba</surname><given-names>P.</given-names></name>; <name><surname>Bates</surname><given-names>M.</given-names></name>; <name><surname>Dar</surname><given-names>O.</given-names></name>; <name><surname>Mattes</surname><given-names>F.</given-names></name>; <name><surname>Kidd</surname><given-names>M.</given-names></name>; <name><surname>Ippolito</surname><given-names>G.</given-names></name>; <name><surname>Azhar</surname><given-names>E. I.</given-names></name>; <name><surname>Zumla</surname><given-names>A.</given-names></name> (<year>2016</year>) <article-title>Rapid spread of Zika virus in the Americas - implications for public health
preparedness for mass gatherings at the 2016 Brazil Olympic Games</article-title>. <source>Int. J. Infect. Dis.</source><volume>44</volume>, <fpage>11</fpage>–<lpage>5</lpage>. <pub-id pub-id-type="doi">10.1016/j.ijid.2016.02.001</pub-id>.<pub-id pub-id-type="pmid">26854199</pub-id></mixed-citation></ref><ref id="ref37"><mixed-citation publication-type="journal" id="cit37"><name><surname>Cao-Lormeau</surname><given-names>V.-M.</given-names></name>; <name><surname>Blake</surname><given-names>A.</given-names></name>; <name><surname>Mons</surname><given-names>S.</given-names></name>; <name><surname>Lastère</surname><given-names>S.</given-names></name>; <name><surname>Roche</surname><given-names>C.</given-names></name>; <name><surname>Vanhomwegen</surname><given-names>J.</given-names></name>; <name><surname>Dub</surname><given-names>T.</given-names></name>; <name><surname>Baudouin</surname><given-names>L.</given-names></name>; <name><surname>Teissier</surname><given-names>A.</given-names></name>; <name><surname>Larre</surname><given-names>P.</given-names></name>; <name><surname>Vial</surname><given-names>A.-L.</given-names></name>; <name><surname>Decam</surname><given-names>C.</given-names></name>; <name><surname>Choumet</surname><given-names>V.</given-names></name>; <name><surname>Halstead</surname><given-names>S. K.</given-names></name>; <name><surname>Willison</surname><given-names>H. J.</given-names></name>; <name><surname>Musset</surname><given-names>L.</given-names></name>; <name><surname>Manuguerra</surname><given-names>J.-C.</given-names></name>; <name><surname>Despres</surname><given-names>P.</given-names></name>; <name><surname>Fournier</surname><given-names>E.</given-names></name>; <name><surname>Mallet</surname><given-names>H.-P.</given-names></name>; <name><surname>Musso</surname><given-names>D.</given-names></name>; <name><surname>Fontanet</surname><given-names>A.</given-names></name>; <name><surname>Neil</surname><given-names>J.</given-names></name>; <name><surname>Ghawché</surname><given-names>F.</given-names></name> (<year>2016</year>) <article-title>Guillain-Barré Syndrome outbreak associated with Zika virus
infection in French Polynesia: a case-control study</article-title>. <source>Lancet</source><volume>387</volume>, <fpage>1531</fpage>–<lpage>1539</lpage>. <pub-id pub-id-type="doi">10.1016/S0140-6736(16)00562-6</pub-id>.<pub-id pub-id-type="pmid">26948433</pub-id></mixed-citation></ref><ref id="ref38"><mixed-citation publication-type="journal" id="cit38"><name><surname>Pantaleao Fontes</surname><given-names>C. A.</given-names></name>; <name><surname>Damas dos Santos</surname><given-names>A. A. S. M.</given-names></name>; <name><surname>Marchiori</surname><given-names>E.</given-names></name> (<year>2016</year>) <article-title>Magnetic resonance imaging findings in Guillain-Barre syndrome caused by
Zika virus infection</article-title>. <source>Neuroradiology</source><volume>58</volume>, <fpage>837</fpage>–<lpage>838</lpage>. <pub-id pub-id-type="doi">10.1007/s00234-016-1687-9</pub-id>.<pub-id pub-id-type="pmid">27067205</pub-id></mixed-citation></ref><ref id="ref39"><mixed-citation publication-type="journal" id="cit39"><name><surname>Chambers</surname><given-names>T. J.</given-names></name>; <name><surname>Grakoui</surname><given-names>A.</given-names></name>; <name><surname>Rice</surname><given-names>C. M.</given-names></name> (<year>1991</year>) <article-title>Processing of the yellow fever virus nonstructural polyprotein: a
catalytically active NS3 proteinase domain and NS2B are required for cleavages at
dibasic sites</article-title>. <source>J. Virol.</source><volume>65</volume>, <fpage>6042</fpage>–<lpage>6050</lpage>. <pub-id pub-id-type="doi">10.1128/JVI.65.11.6042-6050.1991</pub-id>.<pub-id pub-id-type="pmid">1833562</pub-id></mixed-citation></ref><ref id="ref40"><mixed-citation publication-type="journal" id="cit40"><name><surname>Falgout</surname><given-names>B.</given-names></name>; <name><surname>Pethel</surname><given-names>M.</given-names></name>; <name><surname>Zhang</surname><given-names>Y. M.</given-names></name>; <name><surname>Lai</surname><given-names>C. J.</given-names></name> (<year>1991</year>) <article-title>Both nonstructural proteins NS2B and NS3 are required for the proteolytic
processing of dengue virus nonstructural proteins</article-title>. <source>J. Virol.</source><volume>65</volume>, <fpage>2467</fpage>–<lpage>2475</lpage>. <pub-id pub-id-type="doi">10.1128/JVI.65.5.2467-2475.1991</pub-id>.<pub-id pub-id-type="pmid">2016768</pub-id></mixed-citation></ref><ref id="ref41"><mixed-citation publication-type="journal" id="cit41"><name><surname>Luo</surname><given-names>D.</given-names></name>; <name><surname>Vasudevan</surname><given-names>S. G.</given-names></name>; <name><surname>Lescar</surname><given-names>J.</given-names></name> (<year>2015</year>) <article-title>The flavivirus NS2B–NS3 protease–helicase as a target for
antiviral drug development</article-title>. <source>Antiviral Res.</source><volume>118</volume>, <fpage>148</fpage>–<lpage>158</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2015.03.014</pub-id>.<pub-id pub-id-type="pmid">25842996</pub-id></mixed-citation></ref><ref id="ref42"><mixed-citation publication-type="journal" id="cit42"><name><surname>Fang</surname><given-names>J. e.</given-names></name>; <name><surname>Sun</surname><given-names>L.</given-names></name>; <name><surname>Peng</surname><given-names>G.</given-names></name>; <name><surname>Xu</surname><given-names>J.</given-names></name>; <name><surname>Zhou</surname><given-names>R.</given-names></name>; <name><surname>Cao</surname><given-names>S.</given-names></name>; <name><surname>Chen</surname><given-names>H.</given-names></name>; <name><surname>Song</surname><given-names>Y.</given-names></name> (<year>2013</year>) <article-title>Identification of three antiviral inhibitors against japanese encephalitis
virus from library of pharmacologically active compounds 1280</article-title>. <source>PLoS One</source><volume>8</volume>, <fpage>e78425</fpage><pub-id pub-id-type="doi">10.1371/journal.pone.0078425</pub-id>.<pub-id pub-id-type="pmid">24348901</pub-id></mixed-citation></ref><ref id="ref43"><mixed-citation publication-type="weblink" id="cit43"><person-group><collab>World Health
Organization</collab></person-group>. <article-title>Hepatitis C</article-title>. <uri xlink:href="https://www.who.int/news-room/fact-sheets/detail/hepatitis-c">https://www.who.int/news-room/fact-sheets/detail/hepatitis-c</uri> (accessed Jan 29,
2020).</mixed-citation></ref><ref id="ref44"><mixed-citation publication-type="journal" id="cit44"><name><surname>Stachulski</surname><given-names>A. V.</given-names></name>; <name><surname>Pidathala</surname><given-names>C.</given-names></name>; <name><surname>Row</surname><given-names>E. C.</given-names></name>; <name><surname>Sharma</surname><given-names>R.</given-names></name>; <name><surname>Berry</surname><given-names>N. G.</given-names></name>; <name><surname>Lawrenson</surname><given-names>A. S.</given-names></name>; <name><surname>Moores</surname><given-names>S. L.</given-names></name>; <name><surname>Iqbal</surname><given-names>M.</given-names></name>; <name><surname>Bentley</surname><given-names>J.</given-names></name>; <name><surname>Allman</surname><given-names>S. A.</given-names></name>; <name><surname>Edwards</surname><given-names>G.</given-names></name>; <name><surname>Helm</surname><given-names>A.</given-names></name>; <name><surname>Hellier</surname><given-names>J.</given-names></name>; <name><surname>Korba</surname><given-names>B. E.</given-names></name>; <name><surname>Semple</surname><given-names>J. E.</given-names></name>; <name><surname>Rossignol</surname><given-names>J.-F.</given-names></name> (<year>2011</year>) <article-title>Thiazolides as novel antiviral agents. 2. Inhibition of hepatitis C virus
replication</article-title>. <source>J. Med. Chem.</source><volume>54</volume>, <fpage>8670</fpage>–<lpage>8680</lpage>. <pub-id pub-id-type="doi">10.1021/jm201264t</pub-id>.<pub-id pub-id-type="pmid">22059983</pub-id></mixed-citation></ref><ref id="ref45"><mixed-citation publication-type="journal" id="cit45"><name><surname>Korba</surname><given-names>B. E.</given-names></name>; <name><surname>Elazar</surname><given-names>M.</given-names></name>; <name><surname>Lui</surname><given-names>P.</given-names></name>; <name><surname>Rossignol</surname><given-names>J.-F.</given-names></name>; <name><surname>Glenn</surname><given-names>J. S.</given-names></name> (<year>2008</year>) <article-title>Potential for hepatitis C virus resistance to nitazoxanide or
tizoxanide</article-title>. <source>Antimicrob. Agents Chemother.</source><volume>52</volume>, <fpage>4069</fpage>–<lpage>4071</lpage>. <pub-id pub-id-type="doi">10.1128/AAC.00078-08</pub-id>.<pub-id pub-id-type="pmid">18710916</pub-id></mixed-citation></ref><ref id="ref46"><mixed-citation publication-type="journal" id="cit46"><name><surname>Yon</surname><given-names>C.</given-names></name>; <name><surname>Viswanathan</surname><given-names>P.</given-names></name>; <name><surname>Rossignol</surname><given-names>J. F.</given-names></name>; <name><surname>Korba</surname><given-names>B.</given-names></name> (<year>2011</year>) <article-title>Mutations in HCV non-structural genes do not contribute to resistance to
nitazoxanide in replicon-containing cells</article-title>. <source>Antiviral Res.</source><volume>91</volume>, <fpage>233</fpage>–<lpage>240</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2011.05.017</pub-id>.<pub-id pub-id-type="pmid">21703309</pub-id></mixed-citation></ref><ref id="ref47"><mixed-citation publication-type="journal" id="cit47"><name><surname>de Carvalho</surname><given-names>L. P.</given-names></name>; <name><surname>Darby</surname><given-names>C. M.</given-names></name>; <name><surname>Rhee</surname><given-names>K. Y.</given-names></name>; <name><surname>Nathan</surname><given-names>C.</given-names></name> (<year>2011</year>) <article-title>Nitazoxanide disrupts membrane potential and intrabacterial pH homeostasis
of <italic>Mycobacterium tuberculosis</italic></article-title>. <source>ACS Med. Chem. Lett.</source><volume>2</volume>, <fpage>849</fpage>–<lpage>854</lpage>. <pub-id pub-id-type="doi">10.1021/ml200157f</pub-id>.<pub-id pub-id-type="pmid">22096616</pub-id></mixed-citation></ref><ref id="ref48"><mixed-citation publication-type="journal" id="cit48"><name><surname>Madrid</surname><given-names>P. B.</given-names></name>; <name><surname>Panchal</surname><given-names>R. G.</given-names></name>; <name><surname>Warren</surname><given-names>T. K.</given-names></name>; <name><surname>Shurtleff</surname><given-names>A. C.</given-names></name>; <name><surname>Endsley</surname><given-names>A. N.</given-names></name>; <name><surname>Green</surname><given-names>C. E.</given-names></name>; <name><surname>Kolokoltsov</surname><given-names>A.</given-names></name>; <name><surname>Davey</surname><given-names>R.</given-names></name>; <name><surname>Manger</surname><given-names>I. D.</given-names></name>; <name><surname>Gilfillan</surname><given-names>L.</given-names></name>; <name><surname>Bavari</surname><given-names>S.</given-names></name>; <name><surname>Tanga</surname><given-names>M. J.</given-names></name> (<year>2015</year>) <article-title>Evaluation of ebola virus inhibitors for drug repurposing</article-title>. <source>ACS Infect. Dis.</source><volume>1</volume>, <fpage>317</fpage>–<lpage>326</lpage>. <pub-id pub-id-type="doi">10.1021/acsinfecdis.5b00030</pub-id>.<pub-id pub-id-type="pmid">27622822</pub-id></mixed-citation></ref><ref id="ref49"><mixed-citation publication-type="journal" id="cit49"><name><surname>Jacobs</surname><given-names>S. E.</given-names></name>; <name><surname>Lamson</surname><given-names>D. M.</given-names></name>; <name><surname>St George</surname><given-names>K.</given-names></name>; <name><surname>Walsh</surname><given-names>T. J.</given-names></name> (<year>2013</year>) <article-title>Human rhinoviruses</article-title>. <source>Clin. Microbiol. Rev.</source><volume>26</volume>, <fpage>135</fpage>–<lpage>162</lpage>. <pub-id pub-id-type="doi">10.1128/CMR.00077-12</pub-id>.<pub-id pub-id-type="pmid">23297263</pub-id></mixed-citation></ref><ref id="ref50"><mixed-citation publication-type="journal" id="cit50"><name><surname>Jurgeit</surname><given-names>A.</given-names></name>; <name><surname>McDowell</surname><given-names>R.</given-names></name>; <name><surname>Moese</surname><given-names>S.</given-names></name>; <name><surname>Meldrum</surname><given-names>E.</given-names></name>; <name><surname>Schwendener</surname><given-names>R.</given-names></name>; <name><surname>Greber</surname><given-names>U. F.</given-names></name> (<year>2012</year>) <article-title>Niclosamide is a proton carrier and targets acidic endosomes with broad
antiviral effects</article-title>. <source>PLoS Pathog.</source><volume>8</volume>, <fpage>e1002976</fpage><pub-id pub-id-type="doi">10.1371/journal.ppat.1002976</pub-id>.<pub-id pub-id-type="pmid">23133371</pub-id></mixed-citation></ref><ref id="ref51"><mixed-citation publication-type="journal" id="cit51"><name><surname>Wang</surname><given-names>Y.-M.</given-names></name>; <name><surname>Lu</surname><given-names>J.-W.</given-names></name>; <name><surname>Lin</surname><given-names>C.-C.</given-names></name>; <name><surname>Chin</surname><given-names>Y.-F.</given-names></name>; <name><surname>Wu</surname><given-names>T.-Y.</given-names></name>; <name><surname>Lin</surname><given-names>L.-I.</given-names></name>; <name><surname>Lai</surname><given-names>Z.-Z.</given-names></name>; <name><surname>Kuo</surname><given-names>S.-C.</given-names></name>; <name><surname>Ho</surname><given-names>Y.-J.</given-names></name> (<year>2016</year>) <article-title>Antiviral activities of niclosamide and nitazoxanide against chikungunya
virus entry and transmission</article-title>. <source>Antiviral Res.</source><volume>135</volume>, <fpage>81</fpage>–<lpage>90</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2016.10.003</pub-id>.<pub-id pub-id-type="pmid">27742486</pub-id></mixed-citation></ref><ref id="ref52"><mixed-citation publication-type="journal" id="cit52"><name><surname>Marrugal-Lorenzo</surname><given-names>J. A.</given-names></name>; <name><surname>Serna-Gallego</surname><given-names>A.</given-names></name>; <name><surname>Berastegui-Cabrera</surname><given-names>J.</given-names></name>; <name><surname>Pachón</surname><given-names>J.</given-names></name>; <name><surname>Sánchez-Céspedes</surname><given-names>J.</given-names></name> (<year>2019</year>) <article-title>Repositioning salicylanilide anthelmintic drugs to treat adenovirus
infections</article-title>. <source>Sci. Rep.</source><volume>9</volume>, <fpage>17</fpage><pub-id pub-id-type="doi">10.1038/s41598-018-37290-3</pub-id>.<pub-id pub-id-type="pmid">30626902</pub-id></mixed-citation></ref><ref id="ref53"><mixed-citation publication-type="journal" id="cit53"><name><surname>Kutok</surname><given-names>J. L.</given-names></name>; <name><surname>Wang</surname><given-names>F.</given-names></name> (<year>2006</year>) <article-title>Spectrum of Epstein-Barr virus–associated diseases</article-title>. <source>Annu. Rev. Pathol.: Mech. Dis.</source><volume>1</volume>, <fpage>375</fpage>–<lpage>404</lpage>. <pub-id pub-id-type="doi">10.1146/annurev.pathol.1.110304.100209</pub-id>.</mixed-citation></ref><ref id="ref54"><mixed-citation publication-type="journal" id="cit54"><name><surname>Huang</surname><given-names>L.</given-names></name>; <name><surname>Yang</surname><given-names>M.</given-names></name>; <name><surname>Yuan</surname><given-names>Y.</given-names></name>; <name><surname>Li</surname><given-names>X.</given-names></name>; <name><surname>Kuang</surname><given-names>E.</given-names></name> (<year>2017</year>) <article-title>Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting
mTOR activation</article-title>. <source>Antiviral Res.</source><volume>138</volume>, <fpage>68</fpage>–<lpage>78</lpage>. <pub-id pub-id-type="doi">10.1016/j.antiviral.2016.12.002</pub-id>.<pub-id pub-id-type="pmid">27939840</pub-id></mixed-citation></ref><ref id="ref55"><mixed-citation publication-type="journal" id="cit55"><name><surname>Jones</surname><given-names>W. E.</given-names></name> (<year>1979</year>) <article-title>Niclosamide as a treatment for Hymenolepis diminuta and Dipylidium caninum
infection in man</article-title>. <source>Am. J. Trop. Med. Hyg.</source><volume>28</volume>, <fpage>300</fpage>–<lpage>302</lpage>. <pub-id pub-id-type="doi">10.4269/ajtmh.1979.28.300</pub-id>.<pub-id pub-id-type="pmid">572147</pub-id></mixed-citation></ref><ref id="ref56"><mixed-citation publication-type="weblink" id="cit56"><person-group><collab>ClinicalTrails.gov</collab></person-group>. Other terms:
niclosamide. <uri xlink:href="https://clinicaltrials.gov/ct2/results?cond=&term=niclosamide&cntry=&state=&city=&dist=">https://clinicaltrials.gov/ct2/results?cond=&term=niclosamide&cntry=&state=&city=&dist=</uri>(accessed February 27, 2020).</mixed-citation></ref><ref id="ref57"><mixed-citation publication-type="journal" id="cit57"><name><surname>Chang</surname><given-names>Y.-W.</given-names></name>; <name><surname>Yeh</surname><given-names>T.-K.</given-names></name>; <name><surname>Lin</surname><given-names>K.-T.</given-names></name>; <name><surname>Chen</surname><given-names>W.-C.</given-names></name>; <name><surname>Yao</surname><given-names>H.-T.</given-names></name> (<year>2006</year>) <article-title>Pharmacokinetics of anti-SARS-CoV agent niclosamide and its analogs in
rats</article-title>. <source>J. Food Drug Anal.</source><volume>14</volume>, <fpage>329</fpage>–<lpage>333</lpage>.</mixed-citation></ref><ref id="ref58"><mixed-citation publication-type="journal" id="cit58"><name><surname>Xu</surname><given-names>J.</given-names></name>; <name><surname>Berastegui-Cabrera</surname><given-names>J.</given-names></name>; <name><surname>Chen</surname><given-names>H.</given-names></name>; <name><surname>Pachón</surname><given-names>J.</given-names></name>; <name><surname>Zhou</surname><given-names>J.</given-names></name>; <name><surname>Sanchez-Cespedes</surname><given-names>J.</given-names></name> (<year>2020</year>) <article-title>Structure-activity relationship studies on diversified salicylamide
derivatives as potent inhibitors of human adenovirus infection</article-title>. <source>J. Med. Chem.</source><pub-id pub-id-type="doi">10.1021/acs.jmedchem.9b01950</pub-id>.</mixed-citation></ref><ref id="ref59"><mixed-citation publication-type="journal" id="cit59"><name><surname>Mook</surname><given-names>R. A.</given-names></name>; <name><surname>Wang</surname><given-names>J.</given-names></name>; <name><surname>Ren</surname><given-names>X.-R.</given-names></name>; <name><surname>Chen</surname><given-names>M.</given-names></name>; <name><surname>Spasojevic</surname><given-names>I.</given-names></name>; <name><surname>Barak</surname><given-names>L. S.</given-names></name>; <name><surname>Lyerly</surname><given-names>H. K.</given-names></name>; <name><surname>Chen</surname><given-names>W.</given-names></name> (<year>2015</year>) <article-title>Structure–activity studies of Wnt/β-catenin inhibition in the
Niclosamide chemotype: Identification of derivatives with improved drug
exposure</article-title>. <source>Bioorg. Med. Chem.</source><volume>23</volume>, <fpage>5829</fpage>–<lpage>5838</lpage>. <pub-id pub-id-type="doi">10.1016/j.bmc.2015.07.001</pub-id>.<pub-id pub-id-type="pmid">26272032</pub-id></mixed-citation></ref><ref id="ref60"><mixed-citation publication-type="journal" id="cit60"><name><surname>Barbosa</surname><given-names>E. J.</given-names></name>; <name><surname>Löbenberg</surname><given-names>R.</given-names></name>; <name><surname>de Araujo</surname><given-names>G. L. B.</given-names></name>; <name><surname>Bou-Chacra</surname><given-names>N. A.</given-names></name> (<year>2019</year>) <article-title>Niclosamide repositioning for treating cancer: Challenges and nano-based
drug delivery opportunities</article-title>. <source>Eur. J. Pharm. Biopharm.</source><volume>141</volume>, <fpage>58</fpage>–<lpage>69</lpage>. <pub-id pub-id-type="doi">10.1016/j.ejpb.2019.05.004</pub-id>.<pub-id pub-id-type="pmid">31078739</pub-id></mixed-citation></ref><ref id="ref61"><mixed-citation publication-type="journal" id="cit61"><name><surname>Costabile</surname><given-names>G.</given-names></name>; <name><surname>d’Angelo</surname><given-names>I.</given-names></name>; <name><surname>Rampioni</surname><given-names>G.</given-names></name>; <name><surname>Bondì</surname><given-names>R.</given-names></name>; <name><surname>Pompili</surname><given-names>B.</given-names></name>; <name><surname>Ascenzioni</surname><given-names>F.</given-names></name>; <name><surname>Mitidieri</surname><given-names>E.</given-names></name>; <name><surname>d’Emmanuele di Villa Bianca</surname><given-names>R.</given-names></name>; <name><surname>Sorrentino</surname><given-names>R.</given-names></name>; <name><surname>Miro</surname><given-names>A.</given-names></name>; <name><surname>Quaglia</surname><given-names>F.</given-names></name>; <name><surname>Imperi</surname><given-names>F.</given-names></name>; <name><surname>Leoni</surname><given-names>L.</given-names></name>; <name><surname>Ungaro</surname><given-names>F.</given-names></name> (<year>2015</year>) <article-title>Toward repositioning niclosamide for antivirulence therapy of
<italic>Pseudomonas aeruginosa</italic> lung infections: Development of inhalable
formulations through nanosuspension technology</article-title>. <source>Mol. Pharmaceutics</source><volume>12</volume>, <fpage>2604</fpage>–<lpage>2617</lpage>. <pub-id pub-id-type="doi">10.1021/acs.molpharmaceut.5b00098</pub-id>.</mixed-citation></ref><ref id="ref62"><mixed-citation publication-type="journal" id="cit62"><name><surname>Lin</surname><given-names>C.-K.</given-names></name>; <name><surname>Bai</surname><given-names>M.-Y.</given-names></name>; <name><surname>Hu</surname><given-names>T.-M.</given-names></name>; <name><surname>Wang</surname><given-names>Y.-C.</given-names></name>; <name><surname>Chao</surname><given-names>T.-K.</given-names></name>; <name><surname>Weng</surname><given-names>S.-J.</given-names></name>; <name><surname>Huang</surname><given-names>R.-L.</given-names></name>; <name><surname>Su</surname><given-names>P.-H.</given-names></name>; <name><surname>Lai</surname><given-names>H.-C.</given-names></name> (<year>2016</year>) <article-title>Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in
ovarian cancer</article-title>. <source>Oncotarget.</source><volume>7</volume>, <fpage>8993</fpage>–<lpage>9006</lpage>. <pub-id pub-id-type="doi">10.18632/oncotarget.7113</pub-id>.<pub-id pub-id-type="pmid">26848771</pub-id></mixed-citation></ref><ref id="ref63"><mixed-citation publication-type="journal" id="cit63"><name><surname>Wrapp</surname><given-names>D.</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>Goldsmith</surname><given-names>J. A.</given-names></name>; <name><surname>Hsieh</surname><given-names>C.-L.</given-names></name>; <name><surname>Abiona</surname><given-names>O.</given-names></name>; <name><surname>Graham</surname><given-names>B. S.</given-names></name>; <name><surname>McLellan</surname><given-names>J. S.</given-names></name> (<year>2020</year>) <article-title>Cryo-EM structure of the 2019-nCoV spike in the prefusion
conformation</article-title>. <source>Science</source><fpage>eabb2507</fpage><pub-id pub-id-type="doi">10.1126/science.abb2507</pub-id>.</mixed-citation></ref><ref id="ref64"><mixed-citation publication-type="weblink" id="cit64"><person-group person-group-type="allauthors"><name><surname>Cohen</surname><given-names>J.</given-names></name></person-group><article-title>Can an anti-HIV combination or other existing drugs outwit the new
coronavirus?</article-title><uri xlink:href="https://www.sciencemag.org/news/2020/01/can-anti-hiv-combination-or-other-existing-drugs-outwit-new-coronavirus">https://www.sciencemag.org/news/2020/01/can-anti-hiv-combination-or-other-existing-drugs-outwit-new-coronavirus</uri>(accessed Feb 1, 2020).</mixed-citation></ref><ref id="ref65"><mixed-citation publication-type="journal" id="cit65"><name><surname>Li</surname><given-names>G.</given-names></name>; <name><surname>De Clercq</surname><given-names>E.</given-names></name> (<year>2020</year>) <article-title>Therapeutic options for the 2019 novel coronavirus
(2019-nCoV)</article-title>. <source>Nat. Rev. Drug Discovery</source><volume>19</volume>, <fpage>149</fpage>–<lpage>150</lpage>. <pub-id pub-id-type="doi">10.1038/d41573-020-00016-0</pub-id>.<pub-id pub-id-type="pmid">32127666</pub-id></mixed-citation></ref><ref id="ref66"><mixed-citation publication-type="journal" id="cit66"><name><surname>Wang</surname><given-names>M.</given-names></name>; <name><surname>Cao</surname><given-names>R.</given-names></name>; <name><surname>Zhang</surname><given-names>L.</given-names></name>; <name><surname>Yang</surname><given-names>X.</given-names></name>; <name><surname>Liu</surname><given-names>J.</given-names></name>; <name><surname>Xu</surname><given-names>M.</given-names></name>; <name><surname>Shi</surname><given-names>Z.</given-names></name>; <name><surname>Hu</surname><given-names>Z.</given-names></name>; <name><surname>Zhong</surname><given-names>W.</given-names></name>; <name><surname>Xiao</surname><given-names>G.</given-names></name> (<year>2020</year>) <article-title>Remdesivir and chloroquine effectively inhibit the recently emerged novel
coronavirus (2019-nCoV) in vitro</article-title>. <source>Cell Res.</source><volume>30</volume>, <fpage>269</fpage>–<lpage>271</lpage>. <pub-id pub-id-type="doi">10.1038/s41422-020-0282-0</pub-id>.<pub-id pub-id-type="pmid">32020029</pub-id></mixed-citation></ref><ref id="ref67"><mixed-citation publication-type="journal" id="cit67"><name><surname>Zhou</surname><given-names>P.</given-names></name>; <name><surname>Yang</surname><given-names>X.-L.</given-names></name>; <name><surname>Wang</surname><given-names>X.-G.</given-names></name>; <name><surname>Hu</surname><given-names>B.</given-names></name>; <name><surname>Zhang</surname><given-names>L.</given-names></name>; <name><surname>Zhang</surname><given-names>W.</given-names></name>; <name><surname>Si</surname><given-names>H.-R.</given-names></name>; <name><surname>Zhu</surname><given-names>Y.</given-names></name>; <name><surname>Li</surname><given-names>B.</given-names></name>; <name><surname>Huang</surname><given-names>C.-L.</given-names></name>; <name><surname>Chen</surname><given-names>H.-D.</given-names></name>; <name><surname>Chen</surname><given-names>J.</given-names></name>; <name><surname>Luo</surname><given-names>Y.</given-names></name>; <name><surname>Guo</surname><given-names>H.</given-names></name>; <name><surname>Jiang</surname><given-names>R.-D.</given-names></name>; <name><surname>Liu</surname><given-names>M.-Q.</given-names></name>; <name><surname>Chen</surname><given-names>Y.</given-names></name>; <name><surname>Shen</surname><given-names>X.-R.</given-names></name>; <name><surname>Wang</surname><given-names>X.</given-names></name>; <name><surname>Zheng</surname><given-names>X.-S.</given-names></name>; <name><surname>Zhao</surname><given-names>K.</given-names></name>; <name><surname>Chen</surname><given-names>Q.-J.</given-names></name>; <name><surname>Deng</surname><given-names>F.</given-names></name>; <name><surname>Liu</surname><given-names>L.-L.</given-names></name>; <name><surname>Yan</surname><given-names>B.</given-names></name>; <name><surname>Zhan</surname><given-names>F.-X.</given-names></name>; <name><surname>Wang</surname><given-names>Y.-Y.</given-names></name>; <name><surname>Xiao</surname><given-names>G.-F.</given-names></name>; <name><surname>Shi</surname><given-names>Z.-L.</given-names></name> (<year>2020</year>) <article-title>A pneumonia outbreak associated with a new coronavirus of probable bat
origin</article-title>. <source>Nature</source><pub-id pub-id-type="doi">10.1038/s41586-020-2012-7</pub-id>.</mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000035 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000035 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= SrasV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:7098069
|texte= Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic
Potential
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:32125140" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a SrasV1
| This area was generated with Dilib version V0.6.33. |  |