Nucleoside analogues for the treatment of coronavirus infections
Identifieur interne : 001737 ( Pmc/Corpus ); précédent : 001736; suivant : 001738Nucleoside analogues for the treatment of coronavirus infections
Auteurs : Andrea J. Pruijssers ; Mark R. DenisonSource :
- Current Opinion in Virology [ 1879-6257 ] ; 2019.
Abstract
Coronaviruses (CoV) represent current and future risk for pandemic zoonotic infections. Nucleoside analogues are highly active across multiple virus families. CoVs encode a proofreading exoribonuclease that opposes inhibition by many nucleoside analogues. Remdesivir is an adenosine analogue that acts against a broad spectrum of CoVs. Other nucleoside analogues show promise against CoVs.
Url:
DOI: 10.1016/j.coviro.2019.04.002
PubMed: 31125806
PubMed Central: 7102703
Links to Exploration step
PMC:7102703Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Nucleoside analogues for the treatment of coronavirus infections</title><author><name sortKey="Pruijssers, Andrea J" sort="Pruijssers, Andrea J" uniqKey="Pruijssers A" first="Andrea J" last="Pruijssers">Andrea J. Pruijssers</name><affiliation><nlm:aff id="aff0005">Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff0010">Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation></author><author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R" last="Denison">Mark R. Denison</name><affiliation><nlm:aff id="aff0005">Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff0010">Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff0015">Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31125806</idno><idno type="pmc">7102703</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102703</idno><idno type="RBID">PMC:7102703</idno><idno type="doi">10.1016/j.coviro.2019.04.002</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">001737</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001737</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Nucleoside analogues for the treatment of coronavirus infections</title><author><name sortKey="Pruijssers, Andrea J" sort="Pruijssers, Andrea J" uniqKey="Pruijssers A" first="Andrea J" last="Pruijssers">Andrea J. Pruijssers</name><affiliation><nlm:aff id="aff0005">Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff0010">Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation></author><author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R" last="Denison">Mark R. Denison</name><affiliation><nlm:aff id="aff0005">Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff0010">Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation><affiliation><nlm:aff id="aff0015">Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States</nlm:aff></affiliation></author></analytic><series><title level="j">Current Opinion in Virology</title><idno type="ISSN">1879-6257</idno><idno type="eISSN">1879-6265</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Highlights</title><p><list list-type="simple" id="lis0005"><list-item id="lsti0005"><label>•</label><p id="par0005">Coronaviruses (CoV) represent current and future risk for pandemic zoonotic infections.</p></list-item><list-item id="lsti0010"><label>•</label><p id="par0010">Nucleoside analogues are highly active across multiple virus families.</p></list-item><list-item id="lsti0015"><label>•</label><p id="par0015">CoVs encode a proofreading exoribonuclease that opposes inhibition by many nucleoside analogues.</p></list-item><list-item id="lsti0020"><label>•</label><p id="par0020">Remdesivir is an adenosine analogue that acts against a broad spectrum of CoVs.</p></list-item><list-item id="lsti0025"><label>•</label><p id="par0025">Other nucleoside analogues show promise against CoVs.</p></list-item></list></p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Su, S" uniqKey="Su S">S. Su</name></author><author><name sortKey="Wong, G" uniqKey="Wong G">G. Wong</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W. Shi</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="Lai, A C K" uniqKey="Lai A">A.C.K. Lai</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author><author><name sortKey="Liu, W" uniqKey="Liu W">W. Liu</name></author><author><name sortKey="Bi, Y" uniqKey="Bi Y">Y. Bi</name></author><author><name sortKey="Gao, G F" uniqKey="Gao G">G.F. Gao</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Y M" uniqKey="Arabi Y">Y.M. Arabi</name></author><author><name sortKey="Balkhy, H H" uniqKey="Balkhy H">H.H. Balkhy</name></author><author><name sortKey="Hayden, F G" uniqKey="Hayden F">F.G. Hayden</name></author><author><name sortKey="Bouchama, A" uniqKey="Bouchama A">A. Bouchama</name></author><author><name sortKey="Luke, T" uniqKey="Luke T">T. Luke</name></author><author><name sortKey="Baillie, J K" uniqKey="Baillie J">J.K. Baillie</name></author><author><name sortKey="Al Omari, A" uniqKey="Al Omari A">A. Al-Omari</name></author><author><name sortKey="Hajeer, A H" uniqKey="Hajeer A">A.H. Hajeer</name></author><author><name sortKey="Senga, M" uniqKey="Senga M">M. Senga</name></author><author><name sortKey="Denison, M R" uniqKey="Denison M">M.R. Denison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Luo, C M" uniqKey="Luo C">C.-M. Luo</name></author><author><name sortKey="Wang, N" uniqKey="Wang N">N. Wang</name></author><author><name sortKey="Yang, X L" uniqKey="Yang X">X.-L. Yang</name></author><author><name sortKey="Liu, H Z" uniqKey="Liu H">H.-Z. Liu</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Li, B" uniqKey="Li B">B. Li</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B. Hu</name></author><author><name sortKey="Peng, C" uniqKey="Peng C">C. Peng</name></author><author><name sortKey="Geng, Q B" uniqKey="Geng Q">Q.-B. Geng</name></author><author><name sortKey="Zhu, G J" uniqKey="Zhu G">G.-J. Zhu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, H" uniqKey="Chu H">H. Chu</name></author><author><name sortKey="Chan, C M" uniqKey="Chan C">C.-M. Chan</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Yuan, S" uniqKey="Yuan S">S. Yuan</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J. Zhou</name></author><author><name sortKey="Au Yeung, R K H" uniqKey="Au Yeung R">R.K.-H. Au-Yeung</name></author><author><name sortKey="Sze, K H" uniqKey="Sze K">K.-H. Sze</name></author><author><name sortKey="Yang, D" uniqKey="Yang D">D. Yang</name></author><author><name sortKey="Shuai, H" uniqKey="Shuai H">H. Shuai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Modjarrad, K" uniqKey="Modjarrad K">K. Modjarrad</name></author><author><name sortKey="Moorthy, V S" uniqKey="Moorthy V">V.S. Moorthy</name></author><author><name sortKey="Ben Embarek, P" uniqKey="Ben Embarek P">P. Ben Embarek</name></author><author><name sortKey="Van Kerkhove, M" uniqKey="Van Kerkhove M">M. Van Kerkhove</name></author><author><name sortKey="Kim, J" uniqKey="Kim J">J. Kim</name></author><author><name sortKey="Kieny, M P" uniqKey="Kieny M">M.-P. Kieny</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brende, B" uniqKey="Brende B">B. Brende</name></author><author><name sortKey="Farrar, J" uniqKey="Farrar J">J. Farrar</name></author><author><name sortKey="Gashumba, D" uniqKey="Gashumba D">D. Gashumba</name></author><author><name sortKey="Moedas, C" uniqKey="Moedas C">C. Moedas</name></author><author><name sortKey="Mundel, T" uniqKey="Mundel T">T. Mundel</name></author><author><name sortKey="Shiozaki, Y" uniqKey="Shiozaki Y">Y. Shiozaki</name></author><author><name sortKey="Vardhan, H" uniqKey="Vardhan H">H. Vardhan</name></author><author><name sortKey="Wanka, J" uniqKey="Wanka J">J. Wanka</name></author><author><name sortKey="R Ttingen, J A" uniqKey="R Ttingen J">J.-A. Røttingen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mehand, M S" uniqKey="Mehand M">M.S. Mehand</name></author><author><name sortKey="Al Shorbaji, F" uniqKey="Al Shorbaji F">F. Al-Shorbaji</name></author><author><name sortKey="Millett, P" uniqKey="Millett P">P. Millett</name></author><author><name sortKey="Murgue, B" uniqKey="Murgue B">B. Murgue</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perales, C" uniqKey="Perales C">C. Perales</name></author><author><name sortKey="Domingo, E" uniqKey="Domingo E">E. Domingo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eckerle, L D" uniqKey="Eckerle L">L.D. Eckerle</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author><author><name sortKey="Sperry, S M" uniqKey="Sperry S">S.M. Sperry</name></author><author><name sortKey="Choi, L" uniqKey="Choi L">L. Choi</name></author><author><name sortKey="Denison, M R" uniqKey="Denison M">M.R. Denison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, E C" uniqKey="Smith E">E.C. Smith</name></author><author><name sortKey="Blanc, H" uniqKey="Blanc H">H. Blanc</name></author><author><name sortKey="Vignuzzi, M" uniqKey="Vignuzzi M">M. Vignuzzi</name></author><author><name sortKey="Denison, M R" uniqKey="Denison M">M.R. Denison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ferron, F" uniqKey="Ferron F">F. Ferron</name></author><author><name sortKey="Subissi, L" uniqKey="Subissi L">L. Subissi</name></author><author><name sortKey="Silveira De Morais, A T" uniqKey="Silveira De Morais A">A.T. Silveira De Morais</name></author><author><name sortKey="Le, N T T" uniqKey="Le N">N.T.T. Le</name></author><author><name sortKey="Sevajol, M" uniqKey="Sevajol M">M. Sevajol</name></author><author><name sortKey="Gluais, L" uniqKey="Gluais L">L. Gluais</name></author><author><name sortKey="Decroly, E" uniqKey="Decroly E">E. Decroly</name></author><author><name sortKey="Vonrhein, C" uniqKey="Vonrhein C">C. Vonrhein</name></author><author><name sortKey="Bricogne, G" uniqKey="Bricogne G">G. Bricogne</name></author><author><name sortKey="Canard, B" uniqKey="Canard B">B. Canard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tejero, H" uniqKey="Tejero H">H. Tejero</name></author><author><name sortKey="Montero, F" uniqKey="Montero F">F. Montero</name></author><author><name sortKey="Nu O, J C" uniqKey="Nu O J">J.C. Nuño</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Te, H S" uniqKey="Te H">H.S. Te</name></author><author><name sortKey="Randall, G" uniqKey="Randall G">G. Randall</name></author><author><name sortKey="Jensen, D M" uniqKey="Jensen D">D.M. Jensen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jordan, P C" uniqKey="Jordan P">P.C. Jordan</name></author><author><name sortKey="Stevens, S K" uniqKey="Stevens S">S.K. Stevens</name></author><author><name sortKey="Deval, J" uniqKey="Deval J">J. Deval</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, T P" uniqKey="Sheahan T">T.P. Sheahan</name></author><author><name sortKey="Sims, A C" uniqKey="Sims A">A.C. Sims</name></author><author><name sortKey="Graham, R L" uniqKey="Graham R">R.L. Graham</name></author><author><name sortKey="Menachery, V D" uniqKey="Menachery V">V.D. Menachery</name></author><author><name sortKey="Gralinski, L E" uniqKey="Gralinski L">L.E. Gralinski</name></author><author><name sortKey="Case, J B" uniqKey="Case J">J.B. Case</name></author><author><name sortKey="Leist, S R" uniqKey="Leist S">S.R. Leist</name></author><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K. Pyrc</name></author><author><name sortKey="Feng, J Y" uniqKey="Feng J">J.Y. Feng</name></author><author><name sortKey="Trantcheva, I" uniqKey="Trantcheva I">I. Trantcheva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saijo, M" uniqKey="Saijo M">M. Saijo</name></author><author><name sortKey="Morikawa, S" uniqKey="Morikawa S">S. Morikawa</name></author><author><name sortKey="Fukushi, S" uniqKey="Fukushi S">S. Fukushi</name></author><author><name sortKey="Mizutani, T" uniqKey="Mizutani T">T. Mizutani</name></author><author><name sortKey="Hasegawa, H" uniqKey="Hasegawa H">H. Hasegawa</name></author><author><name sortKey="Nagata, N" uniqKey="Nagata N">N. Nagata</name></author><author><name sortKey="Iwata, N" uniqKey="Iwata N">N. Iwata</name></author><author><name sortKey="Kurane, I" uniqKey="Kurane I">I. Kurane</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feld, J J" uniqKey="Feld J">J.J. Feld</name></author><author><name sortKey="Hoofnagle, J H" uniqKey="Hoofnagle J">J.H. Hoofnagle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cameron, C E" uniqKey="Cameron C">C.E. Cameron</name></author><author><name sortKey="Castro, C" uniqKey="Castro C">C. Castro</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="Chan, K H" uniqKey="Chan K">K.-H. Chan</name></author><author><name sortKey="Kao, R Y T" uniqKey="Kao R">R.Y.T. Kao</name></author><author><name sortKey="To, K K W" uniqKey="To K">K.K.W. To</name></author><author><name sortKey="Zheng, B J" uniqKey="Zheng B">B.-J. Zheng</name></author><author><name sortKey="Li, C P Y" uniqKey="Li C">C.P.Y. Li</name></author><author><name sortKey="Li, P T W" uniqKey="Li P">P.T.W. Li</name></author><author><name sortKey="Dai, J" uniqKey="Dai J">J. Dai</name></author><author><name sortKey="Mok, F K Y" uniqKey="Mok F">F.K.Y. Mok</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barnard, D L" uniqKey="Barnard D">D.L. Barnard</name></author><author><name sortKey="Day, C W" uniqKey="Day C">C.W. Day</name></author><author><name sortKey="Bailey, K" uniqKey="Bailey K">K. Bailey</name></author><author><name sortKey="Heiner, M" uniqKey="Heiner M">M. Heiner</name></author><author><name sortKey="Montgomery, R" uniqKey="Montgomery R">R. Montgomery</name></author><author><name sortKey="Lauridsen, L" uniqKey="Lauridsen L">L. Lauridsen</name></author><author><name sortKey="Winslow, S" uniqKey="Winslow S">S. Winslow</name></author><author><name sortKey="Hoopes, J" uniqKey="Hoopes J">J. Hoopes</name></author><author><name sortKey="Jk K, Li" uniqKey="Jk K L">Li JK-K</name></author><author><name sortKey="Lee, J" uniqKey="Lee J">J. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Booth, C M" uniqKey="Booth C">C.M. Booth</name></author><author><name sortKey="Matukas, L M" uniqKey="Matukas L">L.M. Matukas</name></author><author><name sortKey="Tomlinson, G A" uniqKey="Tomlinson G">G.A. Tomlinson</name></author><author><name sortKey="Rachlis, A R" uniqKey="Rachlis A">A.R. Rachlis</name></author><author><name sortKey="Rose, D B" uniqKey="Rose D">D.B. Rose</name></author><author><name sortKey="Dwosh, H A" uniqKey="Dwosh H">H.A. Dwosh</name></author><author><name sortKey="Walmsley, S L" uniqKey="Walmsley S">S.L. Walmsley</name></author><author><name sortKey="Mazzulli, T" uniqKey="Mazzulli T">T. Mazzulli</name></author><author><name sortKey="Avendano, M" uniqKey="Avendano M">M. Avendano</name></author><author><name sortKey="Derkach, P" uniqKey="Derkach P">P. Derkach</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gross, A E" uniqKey="Gross A">A.E. Gross</name></author><author><name sortKey="Bryson, M L" uniqKey="Bryson M">M.L. Bryson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. de Wit</name></author><author><name sortKey="Rasmussen, A L" uniqKey="Rasmussen A">A.L. Rasmussen</name></author><author><name sortKey="Feldmann, F" uniqKey="Feldmann F">F. Feldmann</name></author><author><name sortKey="Okumura, A" uniqKey="Okumura A">A. Okumura</name></author><author><name sortKey="Scott, D P" uniqKey="Scott D">D.P. Scott</name></author><author><name sortKey="Brining, D" uniqKey="Brining D">D. Brining</name></author><author><name sortKey="Bushmaker, T" uniqKey="Bushmaker T">T. Bushmaker</name></author><author><name sortKey="Martellaro, C" uniqKey="Martellaro C">C. Martellaro</name></author><author><name sortKey="Baseler, L" uniqKey="Baseler L">L. Baseler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. de Wit</name></author><author><name sortKey="Martellaro, C" uniqKey="Martellaro C">C. Martellaro</name></author><author><name sortKey="Callison, J" uniqKey="Callison J">J. Callison</name></author><author><name sortKey="Munster, V J" uniqKey="Munster V">V.J. Munster</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H. Feldmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, J A" uniqKey="Al Tawfiq J">J.A. Al-Tawfiq</name></author><author><name sortKey="Momattin, H" uniqKey="Momattin H">H. Momattin</name></author><author><name sortKey="Dib, J" uniqKey="Dib J">J. Dib</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z.A. Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Omrani, A S" uniqKey="Omrani A">A.S. Omrani</name></author><author><name sortKey="Saad, M M" uniqKey="Saad M">M.M. Saad</name></author><author><name sortKey="Baig, K" uniqKey="Baig K">K. Baig</name></author><author><name sortKey="Bahloul, A" uniqKey="Bahloul A">A. Bahloul</name></author><author><name sortKey="Abdul Matin, M" uniqKey="Abdul Matin M">M. Abdul-Matin</name></author><author><name sortKey="Alaidaroos, A Y" uniqKey="Alaidaroos A">A.Y. Alaidaroos</name></author><author><name sortKey="Almakhlafi, G A" uniqKey="Almakhlafi G">G.A. Almakhlafi</name></author><author><name sortKey="Albarrak, M M" uniqKey="Albarrak M">M.M. Albarrak</name></author><author><name sortKey="Memish, Z A" uniqKey="Memish Z">Z.A. Memish</name></author><author><name sortKey="Albarrak, A M" uniqKey="Albarrak A">A.M. Albarrak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shalhoub, S" uniqKey="Shalhoub S">S. Shalhoub</name></author><author><name sortKey="Farahat, F" uniqKey="Farahat F">F. Farahat</name></author><author><name sortKey="Al Jiffri, A" uniqKey="Al Jiffri A">A. Al-Jiffri</name></author><author><name sortKey="Simhairi, R" uniqKey="Simhairi R">R. Simhairi</name></author><author><name sortKey="Shamma, O" uniqKey="Shamma O">O. Shamma</name></author><author><name sortKey="Siddiqi, N" uniqKey="Siddiqi N">N. Siddiqi</name></author><author><name sortKey="Mushtaq, A" uniqKey="Mushtaq A">A. Mushtaq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lo, M K" uniqKey="Lo M">M.K. Lo</name></author><author><name sortKey="Jordan, R" uniqKey="Jordan R">R. Jordan</name></author><author><name sortKey="Arvey, A" uniqKey="Arvey A">A. Arvey</name></author><author><name sortKey="Sudhamsu, J" uniqKey="Sudhamsu J">J. Sudhamsu</name></author><author><name sortKey="Shrivastava Ranjan, P" uniqKey="Shrivastava Ranjan P">P. Shrivastava-Ranjan</name></author><author><name sortKey="Hotard, A L" uniqKey="Hotard A">A.L. Hotard</name></author><author><name sortKey="Flint, M" uniqKey="Flint M">M. Flint</name></author><author><name sortKey="Mcmullan, L K" uniqKey="Mcmullan L">L.K. McMullan</name></author><author><name sortKey="Siegel, D" uniqKey="Siegel D">D. Siegel</name></author><author><name sortKey="Clarke, M O" uniqKey="Clarke M">M.O. Clarke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Warren, T K" uniqKey="Warren T">T.K. Warren</name></author><author><name sortKey="Wells, J" uniqKey="Wells J">J. Wells</name></author><author><name sortKey="Panchal, R G" uniqKey="Panchal R">R.G. Panchal</name></author><author><name sortKey="Stuthman, K S" uniqKey="Stuthman K">K.S. Stuthman</name></author><author><name sortKey="Garza, N L" uniqKey="Garza N">N.L. Garza</name></author><author><name sortKey="Van Tongeren, S A" uniqKey="Van Tongeren S">S.A. Van Tongeren</name></author><author><name sortKey="Dong, L" uniqKey="Dong L">L. Dong</name></author><author><name sortKey="Retterer, C J" uniqKey="Retterer C">C.J. Retterer</name></author><author><name sortKey="Eaton, B P" uniqKey="Eaton B">B.P. Eaton</name></author><author><name sortKey="Pegoraro, G" uniqKey="Pegoraro G">G. Pegoraro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agostini, M L" uniqKey="Agostini M">M.L. Agostini</name></author><author><name sortKey="Andres, E L" uniqKey="Andres E">E.L. Andres</name></author><author><name sortKey="Sims, A C" uniqKey="Sims A">A.C. Sims</name></author><author><name sortKey="Graham, R L" uniqKey="Graham R">R.L. Graham</name></author><author><name sortKey="Sheahan, T P" uniqKey="Sheahan T">T.P. Sheahan</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author><author><name sortKey="Smith, E C" uniqKey="Smith E">E.C. Smith</name></author><author><name sortKey="Case, J B" uniqKey="Case J">J.B. Case</name></author><author><name sortKey="Feng, J Y" uniqKey="Feng J">J.Y. Feng</name></author><author><name sortKey="Jordan, R" uniqKey="Jordan R">R. Jordan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Urakova, N" uniqKey="Urakova N">N. Urakova</name></author><author><name sortKey="Kuznetsova, V" uniqKey="Kuznetsova V">V. Kuznetsova</name></author><author><name sortKey="Crossman, D K" uniqKey="Crossman D">D.K. Crossman</name></author><author><name sortKey="Sokratian, A" uniqKey="Sokratian A">A. Sokratian</name></author><author><name sortKey="Guthrie, D B" uniqKey="Guthrie D">D.B. Guthrie</name></author><author><name sortKey="Kolykhalov, A A" uniqKey="Kolykhalov A">A.A. Kolykhalov</name></author><author><name sortKey="Lockwood, M A" uniqKey="Lockwood M">M.A. Lockwood</name></author><author><name sortKey="Natchus, M G" uniqKey="Natchus M">M.G. Natchus</name></author><author><name sortKey="Crowley, M R" uniqKey="Crowley M">M.R. Crowley</name></author><author><name sortKey="Painter, G R" uniqKey="Painter G">G.R. Painter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ehteshami, M" uniqKey="Ehteshami M">M. Ehteshami</name></author><author><name sortKey="Tao, S" uniqKey="Tao S">S. Tao</name></author><author><name sortKey="Zandi, K" uniqKey="Zandi K">K. Zandi</name></author><author><name sortKey="Hsiao, H M" uniqKey="Hsiao H">H.-M. Hsiao</name></author><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Hammond, E" uniqKey="Hammond E">E. Hammond</name></author><author><name sortKey="Amblard, F" uniqKey="Amblard F">F. Amblard</name></author><author><name sortKey="Russell, O O" uniqKey="Russell O">O.O. Russell</name></author><author><name sortKey="Merits, A" uniqKey="Merits A">A. Merits</name></author><author><name sortKey="Schinazi, R F" uniqKey="Schinazi R">R.F. Schinazi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoon, J J" uniqKey="Yoon J">J.-J. Yoon</name></author><author><name sortKey="Toots, M" uniqKey="Toots M">M. Toots</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S. Lee</name></author><author><name sortKey="Lee, M E" uniqKey="Lee M">M.-E. Lee</name></author><author><name sortKey="Ludeke, B" uniqKey="Ludeke B">B. Ludeke</name></author><author><name sortKey="Luczo, J M" uniqKey="Luczo J">J.M. Luczo</name></author><author><name sortKey="Ganti, K" uniqKey="Ganti K">K. Ganti</name></author><author><name sortKey="Cox, R M" uniqKey="Cox R">R.M. Cox</name></author><author><name sortKey="Sticher, Z M" uniqKey="Sticher Z">Z.M. Sticher</name></author><author><name sortKey="Edpuganti, V" uniqKey="Edpuganti V">V. Edpuganti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pyrc, K" uniqKey="Pyrc K">K. Pyrc</name></author><author><name sortKey="Bosch, B J" uniqKey="Bosch B">B.J. Bosch</name></author><author><name sortKey="Berkhout, B" uniqKey="Berkhout B">B. Berkhout</name></author><author><name sortKey="Jebbink, M F" uniqKey="Jebbink M">M.F. Jebbink</name></author><author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R. Dijkman</name></author><author><name sortKey="Rottier, P" uniqKey="Rottier P">P. Rottier</name></author><author><name sortKey="Van Der Hoek, L" uniqKey="Van Der Hoek L">L. van der Hoek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stuyver, L J" uniqKey="Stuyver L">L.J. Stuyver</name></author><author><name sortKey="Whitaker, T" uniqKey="Whitaker T">T. Whitaker</name></author><author><name sortKey="Mcbrayer, T R" uniqKey="Mcbrayer T">T.R. McBrayer</name></author><author><name sortKey="Hernandez Santiago, B I" uniqKey="Hernandez Santiago B">B.I. Hernandez-Santiago</name></author><author><name sortKey="Lostia, S" uniqKey="Lostia S">S. Lostia</name></author><author><name sortKey="Tharnish, P M" uniqKey="Tharnish P">P.M. Tharnish</name></author><author><name sortKey="Ramesh, M" uniqKey="Ramesh M">M. Ramesh</name></author><author><name sortKey="Chu, C K" uniqKey="Chu C">C.K. Chu</name></author><author><name sortKey="Jordan, R" uniqKey="Jordan R">R. Jordan</name></author><author><name sortKey="Shi, J" uniqKey="Shi J">J. Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barnard, D L" uniqKey="Barnard D">D.L. Barnard</name></author><author><name sortKey="Hubbard, V D" uniqKey="Hubbard V">V.D. Hubbard</name></author><author><name sortKey="Burton, J" uniqKey="Burton J">J. Burton</name></author><author><name sortKey="Smee, D F" uniqKey="Smee D">D.F. Smee</name></author><author><name sortKey="Morrey, J D" uniqKey="Morrey J">J.D. Morrey</name></author><author><name sortKey="Otto, M J" uniqKey="Otto M">M.J. Otto</name></author><author><name sortKey="Sidwell, R W" uniqKey="Sidwell R">R.W. Sidwell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taylor, R" uniqKey="Taylor R">R. Taylor</name></author><author><name sortKey="Kotian, P" uniqKey="Kotian P">P. Kotian</name></author><author><name sortKey="Warren, T" uniqKey="Warren T">T. Warren</name></author><author><name sortKey="Panchal, R" uniqKey="Panchal R">R. Panchal</name></author><author><name sortKey="Bavari, S" uniqKey="Bavari S">S. Bavari</name></author><author><name sortKey="Julander, J" uniqKey="Julander J">J. Julander</name></author><author><name sortKey="Dobo, S" uniqKey="Dobo S">S. Dobo</name></author><author><name sortKey="Rose, A" uniqKey="Rose A">A. Rose</name></author><author><name sortKey="El Kattan, Y" uniqKey="El Kattan Y">Y. El-Kattan</name></author><author><name sortKey="Taubenheim, B" uniqKey="Taubenheim B">B. Taubenheim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dyall, J" uniqKey="Dyall J">J. Dyall</name></author><author><name sortKey="Coleman, C M" uniqKey="Coleman C">C.M. Coleman</name></author><author><name sortKey="Hart, B J" uniqKey="Hart B">B.J. Hart</name></author><author><name sortKey="Venkataraman, T" uniqKey="Venkataraman T">T. Venkataraman</name></author><author><name sortKey="Holbrook, M R" uniqKey="Holbrook M">M.R. Holbrook</name></author><author><name sortKey="Kindrachuk, J" uniqKey="Kindrachuk J">J. Kindrachuk</name></author><author><name sortKey="Johnson, R F" uniqKey="Johnson R">R.F. Johnson</name></author><author><name sortKey="Olinger, G G" uniqKey="Olinger G">G.G. Olinger</name></author><author><name sortKey="Jahrling, P B" uniqKey="Jahrling P">P.B. Jahrling</name></author><author><name sortKey="Laidlaw, M" uniqKey="Laidlaw M">M. Laidlaw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Peters, H L" uniqKey="Peters H">H.L. Peters</name></author><author><name sortKey="Jochmans, D" uniqKey="Jochmans D">D. Jochmans</name></author><author><name sortKey="De Wilde, A H" uniqKey="De Wilde A">A.H. de Wilde</name></author><author><name sortKey="Posthuma, C C" uniqKey="Posthuma C">C.C. Posthuma</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author><author><name sortKey="Neyts, J" uniqKey="Neyts J">J. Neyts</name></author><author><name sortKey="Seley Radtke, K L" uniqKey="Seley Radtke K">K.L. Seley-Radtke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Deval, J" uniqKey="Deval J">J. Deval</name></author><author><name sortKey="Fung, A" uniqKey="Fung A">A. Fung</name></author><author><name sortKey="Stevens, S K" uniqKey="Stevens S">S.K. Stevens</name></author><author><name sortKey="Jordan, P C" uniqKey="Jordan P">P.C. Jordan</name></author><author><name sortKey="Gromova, T" uniqKey="Gromova T">T. Gromova</name></author><author><name sortKey="Taylor, J S" uniqKey="Taylor J">J.S. Taylor</name></author><author><name sortKey="Hong, J" uniqKey="Hong J">J. Hong</name></author><author><name sortKey="Meng, J" uniqKey="Meng J">J. Meng</name></author><author><name sortKey="Wang, G" uniqKey="Wang G">G. Wang</name></author><author><name sortKey="Dyatkina, N" uniqKey="Dyatkina N">N. Dyatkina</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eyer, L" uniqKey="Eyer L">L. Eyer</name></author><author><name sortKey="Kondo, H" uniqKey="Kondo H">H. Kondo</name></author><author><name sortKey="Zouharova, D" uniqKey="Zouharova D">D. Zouharova</name></author><author><name sortKey="Hirano, M" uniqKey="Hirano M">M. Hirano</name></author><author><name sortKey="Valdes, J J" uniqKey="Valdes J">J.J. Valdés</name></author><author><name sortKey="Muto, M" uniqKey="Muto M">M. Muto</name></author><author><name sortKey="Kastl, T" uniqKey="Kastl T">T. Kastl</name></author><author><name sortKey="Kobayashi, S" uniqKey="Kobayashi S">S. Kobayashi</name></author><author><name sortKey="Haviernik, J" uniqKey="Haviernik J">J. Haviernik</name></author><author><name sortKey="Igarashi, M" uniqKey="Igarashi M">M. Igarashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Diphoko, T" uniqKey="Diphoko T">T. Diphoko</name></author><author><name sortKey="Gaseitsiwe, S" uniqKey="Gaseitsiwe S">S. Gaseitsiwe</name></author><author><name sortKey="Kasvosve, I" uniqKey="Kasvosve I">I. Kasvosve</name></author><author><name sortKey="Moyo, S" uniqKey="Moyo S">S. Moyo</name></author><author><name sortKey="Okatch, H" uniqKey="Okatch H">H. Okatch</name></author><author><name sortKey="Musonda, R" uniqKey="Musonda R">R. Musonda</name></author><author><name sortKey="Wainberg, M" uniqKey="Wainberg M">M. Wainberg</name></author><author><name sortKey="Makhema, J" uniqKey="Makhema J">J. Makhema</name></author><author><name sortKey="Marlink, R" uniqKey="Marlink R">R. Marlink</name></author><author><name sortKey="Novitsky, V" uniqKey="Novitsky V">V. Novitsky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Valdes, J J" uniqKey="Valdes J">J.J. Valdés</name></author><author><name sortKey="Butterill, P T" uniqKey="Butterill P">P.T. Butterill</name></author><author><name sortKey="Ruzek, D" uniqKey="Ruzek D">D. Růžek</name></author></analytic></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="Liang, R" uniqKey="Liang R">R. Liang</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Zhang, N" uniqKey="Zhang N">N. Zhang</name></author><author><name sortKey="Deng, X" uniqKey="Deng X">X. Deng</name></author><author><name sortKey="Su, M" uniqKey="Su M">M. Su</name></author><author><name sortKey="Su, Y" uniqKey="Su Y">Y. Su</name></author><author><name sortKey="Hu, L" uniqKey="Hu L">L. Hu</name></author><author><name sortKey="He, C" uniqKey="He C">C. He</name></author><author><name sortKey="Ying, T" uniqKey="Ying T">T. Ying</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, K W" uniqKey="Huang K">K.-W. Huang</name></author><author><name sortKey="Hsu, K C" uniqKey="Hsu K">K.-C. Hsu</name></author><author><name sortKey="Chu, L Y" uniqKey="Chu L">L.-Y. Chu</name></author><author><name sortKey="Yang, J M" uniqKey="Yang J">J.-M. Yang</name></author><author><name sortKey="Yuan, H S" uniqKey="Yuan H">H.S. Yuan</name></author><author><name sortKey="Hsiao, Y Y" uniqKey="Hsiao Y">Y.-Y. Hsiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gralinski, L E" uniqKey="Gralinski L">L.E. Gralinski</name></author><author><name sortKey="Baric, R S" uniqKey="Baric R">R.S. Baric</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Y M" uniqKey="Arabi Y">Y.M. Arabi</name></author><author><name sortKey="Alothman, A" uniqKey="Alothman A">A. Alothman</name></author><author><name sortKey="Balkhy, H H" uniqKey="Balkhy H">H.H. Balkhy</name></author><author><name sortKey="Al Dawood, A" uniqKey="Al Dawood A">A. Al-Dawood</name></author><author><name sortKey="Aljohani, S" uniqKey="Aljohani S">S. AlJohani</name></author><author><name sortKey="Al Harbi, S" uniqKey="Al Harbi S">S. Al Harbi</name></author><author><name sortKey="Kojan, S" uniqKey="Kojan S">S. Kojan</name></author><author><name sortKey="Al Jeraisy, M" uniqKey="Al Jeraisy M">M. Al Jeraisy</name></author><author><name sortKey="Deeb, A M" uniqKey="Deeb A">A.M. Deeb</name></author><author><name sortKey="Assiri, A M" uniqKey="Assiri A">A.M. Assiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, F" uniqKey="Chen F">F. Chen</name></author><author><name sortKey="Chan, K H" uniqKey="Chan K">K.H. Chan</name></author><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Kao, R Y T" uniqKey="Kao R">R.Y.T. Kao</name></author><author><name sortKey="Lu, H T" uniqKey="Lu H">H.T. Lu</name></author><author><name sortKey="Fan, K W" uniqKey="Fan K">K.W. Fan</name></author><author><name sortKey="Cheng, V C C" uniqKey="Cheng V">V.C.C. Cheng</name></author><author><name sortKey="Tsui, W H W" uniqKey="Tsui W">W.H.W. Tsui</name></author><author><name sortKey="Hung, I F N" uniqKey="Hung I">I.F.N. Hung</name></author><author><name sortKey="Lee, T S W" uniqKey="Lee T">T.S.W. Lee</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Curr Opin Virol</journal-id><journal-id journal-id-type="iso-abbrev">Curr Opin Virol</journal-id><journal-title-group><journal-title>Current Opinion in Virology</journal-title></journal-title-group><issn pub-type="ppub">1879-6257</issn><issn pub-type="epub">1879-6265</issn><publisher><publisher-name>Published by Elsevier B.V.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31125806</article-id><article-id pub-id-type="pmc">7102703</article-id><article-id pub-id-type="publisher-id">S1879-6257(19)30001-X</article-id><article-id pub-id-type="doi">10.1016/j.coviro.2019.04.002</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Nucleoside analogues for the treatment of coronavirus infections</article-title></title-group><contrib-group><contrib contrib-type="author" id="aut0005"><name><surname>Pruijssers</surname><given-names>Andrea J</given-names></name><xref rid="aff0005" ref-type="aff">1</xref><xref rid="aff0010" ref-type="aff">2</xref></contrib><contrib contrib-type="author" id="aut0010"><name><surname>Denison</surname><given-names>Mark R</given-names></name><email>mark.denison@vumc.org</email><xref rid="aff0005" ref-type="aff">1</xref><xref rid="aff0010" ref-type="aff">2</xref><xref rid="aff0015" ref-type="aff">3</xref></contrib></contrib-group><aff id="aff0005"><label>1</label>Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States</aff><aff id="aff0010"><label>2</label>Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, United States</aff><aff id="aff0015"><label>3</label>Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States</aff><pub-date pub-type="pmc-release"><day>21</day><month>5</month><year>2019</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>4</month><year>2019</year></pub-date><pub-date pub-type="epub"><day>21</day><month>5</month><year>2019</year></pub-date><volume>35</volume><fpage>57</fpage><lpage>62</lpage><permissions><copyright-statement>© 2019 Published by Elsevier B.V.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder></copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract abstract-type="author-highlights" id="abs0005"><title>Highlights</title><p><list list-type="simple" id="lis0005"><list-item id="lsti0005"><label>•</label><p id="par0005">Coronaviruses (CoV) represent current and future risk for pandemic zoonotic infections.</p></list-item><list-item id="lsti0010"><label>•</label><p id="par0010">Nucleoside analogues are highly active across multiple virus families.</p></list-item><list-item id="lsti0015"><label>•</label><p id="par0015">CoVs encode a proofreading exoribonuclease that opposes inhibition by many nucleoside analogues.</p></list-item><list-item id="lsti0020"><label>•</label><p id="par0020">Remdesivir is an adenosine analogue that acts against a broad spectrum of CoVs.</p></list-item><list-item id="lsti0025"><label>•</label><p id="par0025">Other nucleoside analogues show promise against CoVs.</p></list-item></list></p></abstract><abstract id="abs0010"><p>Recent outbreaks of SARS-Coronavirus and MERS-Coronavirus (CoV) have heightened awareness about the lack of vaccines or antiviral compounds approved for prevention or treatment of human or potential zoonotic CoVs. Anti-CoV drug development has long been challenged by the activity of a 3′ to 5′ proofreading exoribonuclease unique to CoVs. Recently, a promising nucleoside analogue with broad-spectrum activity against CoVs has been identified. This review will discuss progress made in the development of antiviral nucleoside and nucleotide analogues targeting viral RNA synthesis as effective therapeutics against CoV infections and propose promising strategies for combination therapy.</p></abstract></article-meta></front><body><p id="par0150"><boxed-text id="tb0005"><p id="par0030"><bold>Current Opinion in Virology</bold> 2019, <bold>35</bold>:57–62</p><p id="par0035">This review comes from a themed issue on <bold>Antiviral strategies</bold></p><p id="par0040">Edited by <bold>Margo A Brinton</bold> and <bold>Richard K Plemper</bold></p><p id="par0045">For a complete overview see the <ext-link ext-link-type="uri" xlink:href="http://www.sciencedirect.com/science/journal/18796257/35" id="intr0005"><underline>Issue</underline></ext-link> and the <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.coviro.2019.05.011" id="intr0010"><underline>Editorial</underline></ext-link></p><p id="par0050">Available online 21st May 2019</p><p id="par0055"><ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.coviro.2019.04.002" id="intr0015"><bold>https://doi.org/10.1016/j.coviro.2019.04.002</bold></ext-link></p><p id="par0060">1879-6257/© 2019 Published by Elsevier B.V.</p></boxed-text></p><sec id="sec0005"><title>Introduction</title><p id="par0065">Coronaviruses (CoVs) are a family of enveloped viruses containing a positive-sense RNA genome. CoVs belong to the family <italic>Coronaviridae</italic> within the order <italic>Nidovirales</italic>. The <italic>Coronaviridae</italic>, henceforth referred to as CoVs, infect a broad range of vertebrates including mammals and birds. Of the six CoV strains isolated from humans, four strains (HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43) cause a usually mild self-limiting upper respiratory infection accounting for an estimated 15–29% of common colds [<xref rid="bib0005" ref-type="bibr">1</xref>]. Two other human CoV strains have produced more serious respiratory disease epidemics in recent years. Severe acute respiratory syndrome (SARS)-CoV originated in China in 2002 and 2003 and spread to a total of 37 countries, causing more than 8000 cases of SARS with an estimated fatality rate of 9% [<xref rid="bib0010" ref-type="bibr">2</xref>]. The cause of an ongoing epidemic of Middle East respiratory syndrome, MERS-CoV was first identified in Saudi Arabia in 2012 and to date has caused more than 2374 cases in 27 countries with a fatality rate >34% [<xref rid="bib0015" ref-type="bibr">3</xref>,<xref rid="bib0020" ref-type="bibr">4</xref>]. The use of human host cell receptors by both human and bat CoVs supports predictions of significant risk for emergence of new potential pandemic zoonotic CoVs [<xref rid="bib0025" ref-type="bibr">5</xref>,<xref rid="bib0030" ref-type="bibr">6</xref>]. Notably, no vaccines or antiviral compounds are approved for prevention or treatment of human or potential zoonotic CoVs. Emerging CoVs have been accorded priority status by WHO and government agencies for development of prevention and treatment strategies due to severity of these infections and credible pandemic potential [<xref rid="bib0035" ref-type="bibr">7</xref>, <xref rid="bib0040" ref-type="bibr">8</xref>, <xref rid="bib0045" ref-type="bibr">9</xref>]. This review will focus on opportunities for and challenges to development of antiviral nucleoside and nucleotide analogues targeting viral RNA synthesis as effective therapeutics against CoV infections.</p></sec><sec id="sec0010"><title>CoV antiviral strategies</title><p id="par0070">Drugs currently under investigation for use against CoV disease include monoclonal antibodies; direct-acting antivirals (DAAs) including as protease, helicase, and polymerase inhibitors; and immunomodulators such as interferons and corticosteroids. Challenges to CoV antivirals development are both general to RNA viruses and specific to CoVs. The replication of positive-sense RNA virus genomes is generally characterized by high error rates, high viral yields, short replication times, and abundant homologous and nonhomologous recombination [<xref rid="bib0050" ref-type="bibr">10</xref>]. In consequence, ‘viral swarms’ are generated which consist of a diverse population of genome mutants with varying degrees of fitness. This genetic plasticity challenges development of broadly useful antivirals by enabling rapid development of drug resistance while preserving overall viral fitness.</p><p id="par0075">Development of nucleoside analogue inhibitors of CoVs is further hampered by the novel RNA-dependent RNA proofreading activity of CoV nonstructural protein 14, a 3′ to 5′ exoribonuclease (nsp14-ExoN), which confers up to 20-fold increase in replication fidelity compared with other RNA viruses. The nsp14-ExoN activity is responsible for native CoV high resistance to many nucleoside analogues including ribavirin and 5-fluorouracil [<xref rid="bib0055" ref-type="bibr">11</xref>, <xref rid="bib0060" ref-type="bibr">12</xref>, <xref rid="bib0065" ref-type="bibr">13</xref>]. Nevertheless, the recent development of nucleotide and nucleoside analogue inhibitors with a high barrier for resistance, broad-spectrum activity against multiple CoVs, and the ability to inhibit WT CoVs in the presence of nsp14-ExoN holds promise for the treatment of CoV disease.</p></sec><sec id="sec0015"><title>Nucleotide and nucleoside analogue inhibitors for the treatment of CoV infections</title><p id="par0080">Nucleotide and nucleoside analogue inhibitors, hereafter abbreviated NI, are chemically synthesized analogues of purines and pyrimidines in which the heterocyclic ring or sugar moiety has been altered. Currently used to treat both chronic and acute viral infections, NIs are administered as nucleotide or nucleoside precursors or prodrugs, which are metabolized by host or viral kinases to their active triphosphate once inside the cell.</p><p id="par0085">NIs exert inhibitory effects on viral replication by one or more non-mutually exclusive mechanisms (<xref rid="fig0005" ref-type="fig">Figure 1</xref>). First, mis-incorporation of foreign nucleotides in replicating viral genomes may cause chain termination and disrupt subsequent replication or transcription. Chain termination may be immediate (obligate) or may occur following a limited extent of continued RNA or DNA synthesis (non-obligate). Second, NIs may incorporate into elongating nucleotide chains, mispairing with and/or substituting natural nucleotides, thereby introducing mutations that potentially impair RNA synthesis, structure, or RNA–protein interactions or protein functions. Accumulation of mutations and loss of virus viability are referred to as lethal mutagenesis and error catastrophe [<xref rid="bib0070" ref-type="bibr">14</xref>]. Through these mechanisms, NIs alter the genetic makeup of the virus, leading to a decrease in viral fitness with every consecutive replication cycle. Finally, NIs may cause depletion of pools of naturally occurring nucleotides by mimicking [<xref rid="bib0075" ref-type="bibr">15</xref>].<fig id="fig0005"><label>Figure 1</label><caption><p>Mechanisms of inhibition by nucleoside and nucleotide analogues. Schematic representation illustrates normal replication by the RdRp (blue sphere), premature chain termination caused by an obligate chain terminator, reduced replication fidelity due to mutagen incorporation, and depletion of pools of naturally occurring nucleotides.</p></caption><alt-text id="at0115">Figure 1</alt-text><graphic xlink:href="gr1_lrg"></graphic></fig></p><p id="par0090">NIs demonstrate a relatively high barrier to resistance emergence because the structural conservation of the binding site of their polymerase targets is high among virus families, and resistance mutations generally incur a fitness cost for the enzyme and the virus [<xref rid="bib0080" ref-type="bibr">16</xref>]. For CoVs, amino acid conservation of the viral RdRp ranges from 70 to near 100% and is maintained across genera, suggesting NIs could potentially serve as broad-spectrum inhibitors of CoV infection [<xref rid="bib0085" ref-type="bibr">17<sup>••</sup></xref>]. However, proofreading activity of nsp14-ExoN activity protects CoVs from many NIs effective against other RNA viruses [<xref rid="bib0060" ref-type="bibr">12</xref>,<xref rid="bib0090" ref-type="bibr">18</xref>]. To effectively inhibit CoVs, an NI needs to either evade recognition by ExoN or undergo uptake into the elongating strand at a rate exceeding ExoN excision kinetics. We will next discuss several antiviral NIs described in the literature and evidence supporting their efficacy against CoVs.</p><p id="par0095"><underline>Ribavirin</underline> (1-β-<sc>d</sc>-ribofuranosyl-1, 2,4-triazole-3-carboxyamide) is a guanosine analogue with broad-spectrum antiviral activity against RNA viruses. It is used to treat hepatitis C and E virus, respiratory syncytial virus, Lassa virus, and hantavirus infections. In its monophosphate form, ribavirin interactions with inosine monophosphate dehydrogenase (IMPDH), a host enzyme vital to nucleotide biosynthesis, result in decreased guanosine production leading to inhibition of viral RNA synthesis though depletion of cellular GTP pools [<xref rid="bib0095" ref-type="bibr">19</xref>]. Furthermore, incorporation of its triphosphate form by the viral polymerase leads to lethal mutagenesis [<xref rid="bib0100" ref-type="bibr">20</xref>]. The proofreading activity of ExoN leaves CoVs impervious to doses of ribavirin that inhibit other viruses effectively [<xref rid="bib0060" ref-type="bibr">12</xref>]. Although high dose ribavirin showed partial inhibition of SARS-CoV and MERS-CoV replication <italic>in vitro</italic> (<xref rid="tbl0005" ref-type="table">Table 1</xref>) [<xref rid="bib0090" ref-type="bibr">18</xref>,<xref rid="bib0105" ref-type="bibr">21</xref>], drug treatment increased viral load and exacerbated disease in a mouse model of SARS-CoV disease [<xref rid="bib0110" ref-type="bibr">22</xref>]. Ribavirin treatment did not improve the clinical outcome of SARS-CoV disease in human subjects and caused significant toxicity [<xref rid="bib0115" ref-type="bibr">23</xref>,<xref rid="bib0120" ref-type="bibr">24</xref>]. Synergistic activity against MERS-CoV of ribavirin combined with IFNα2b was observed <italic>in vitro</italic> and in rhesus macaques, suggesting that IFN increases the potency of ribavirin at lower, more tolerable concentrations [<xref rid="bib0125" ref-type="bibr">25</xref>,<xref rid="bib0130" ref-type="bibr">26</xref>]. However, five critically ill MERS-CoV-positive patients who were treated with a combination of ribavirin and IFNα2b showed no clinical improvement [<xref rid="bib0135" ref-type="bibr">27</xref>]. Treatment of 20 MERS patients with a combination of ribavirin and IFNα2a showed significantly improved survival at 14 days but not at 28 days [<xref rid="bib0140" ref-type="bibr">28</xref>], whereas treatment of MERS patients with a combination of IFNα2a or IFNβ1a and ribavirin yielded no survival benefit in another study [<xref rid="bib0145" ref-type="bibr">29</xref>]. Thus, although ribavirin shows some efficacy <italic>in vitro</italic>, it does not provide clinical benefit to humans with SARS-CoV or MERS-CoV infections.<table-wrap position="float" id="tbl0005"><label>Table 1</label><caption><p>Nucleoside analogues with demonstrated activity against human CoVs</p></caption><alt-text id="at0120">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th align="left">Nucleoside analogue</th><th align="left">EC50 or IC50</th><th align="left">Citation</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="2">Ribavirin</td><td align="left">50–819 μM (SARS-CoV)</td><td align="left" valign="middle" rowspan="2">[<xref rid="bib0105" ref-type="bibr">21</xref>,<xref rid="bib0255" ref-type="bibr">51</xref>]</td></tr><tr><td align="left">20 μM (MERS-CoV)</td></tr><tr><td colspan="3" align="left">
</td></tr><tr><td align="left" valign="middle" rowspan="3">Remdesivir</td><td align="left">0.07 μM (SARS-CoV)</td><td align="left" valign="middle" rowspan="3">[<xref rid="bib0085" ref-type="bibr">17<sup>••</sup></xref>,<xref rid="bib0160" ref-type="bibr">32<sup>••</sup></xref>]</td></tr><tr><td align="left">0.03–0.07 μM (MERS-CoV)</td></tr><tr><td align="left">0.03 μM (MHV)</td></tr><tr><td colspan="3" align="left">
</td></tr><tr><td align="left" valign="middle" rowspan="2">β-<sc>d</sc>-N4-hydroxycytidine</td><td align="left">0.4 μM (HCoV-NL63)</td><td align="left" valign="middle" rowspan="2">[<xref rid="bib0180" ref-type="bibr">36</xref>,<xref rid="bib0190" ref-type="bibr">38</xref>]</td></tr><tr><td align="left">5 μM (SARS-CoV)</td></tr><tr><td colspan="3" align="left">
</td></tr><tr><td align="left" valign="middle" rowspan="2">BCX4430</td><td align="left">68.4 μM (MERS-CoV)</td><td align="left" valign="middle" rowspan="2">[<xref rid="bib0155" ref-type="bibr">31</xref>]</td></tr><tr><td align="left">57.7 μM (SARS-CoV)</td></tr><tr><td colspan="3" align="left">
</td></tr><tr><td align="left" valign="middle" rowspan="2">Gemcitabine hydrochloride</td><td align="left">1.22 μM (MERS-CoV)</td><td align="left" valign="middle" rowspan="2">[<xref rid="bib0200" ref-type="bibr">40</xref>]</td></tr><tr><td align="left">4.96 μM (SARS-CoV)</td></tr><tr><td colspan="3" align="left">
</td></tr><tr><td align="left">6-Azauridine</td><td align="left">0.03 μM (HCoV-NL63)</td><td align="left">[<xref rid="bib0180" ref-type="bibr">36</xref>]</td></tr><tr><td colspan="3" align="left">
</td></tr><tr><td align="left" valign="middle" rowspan="2">Mizoribine</td><td align="left">13.5 μM (MERS-CoV)</td><td align="left" valign="middle" rowspan="2">[<xref rid="bib0090" ref-type="bibr">18</xref>]</td></tr><tr><td align="left">62 μM (SARS-CoV)</td></tr><tr><td colspan="3" align="left">
</td></tr><tr><td align="left" valign="middle" rowspan="2">Acyclovir fleximer</td><td align="left">23 μM (MERS-CoV)</td><td align="left" valign="middle" rowspan="2">[<xref rid="bib0205" ref-type="bibr">41</xref>]</td></tr><tr><td align="left">8.8 μM (HCoV-NL63)</td></tr></tbody></table></table-wrap></p><p id="par0100"><underline>Remdesivir (Gilead Science (GS)-5734)</underline> is a phosphoramidate prodrug of the adenosine NI GS-441524 which is effective against filoviruses, pneumoviruses, and paramyxoviruses and is currently in a Phase I dose-escalation trial for Ebola virus infection [<xref rid="bib0150" ref-type="bibr">30</xref>]. Biochemical studies indicate that remdesivir acts as a non-obligate chain terminator [<xref rid="bib0155" ref-type="bibr">31</xref>]. Remdesivir is effective against a broad spectrum of human and pre-epidemic zoonotic CoVs and potently inhibits replication of SARS-CoV and MERS-CoV in primary human airway epithelial cultures (<xref rid="tbl0005" ref-type="table">Table 1</xref>) [<xref rid="bib0085" ref-type="bibr">17<sup>••</sup></xref>,<xref rid="bib0160" ref-type="bibr">32<sup>••</sup></xref>]. Mice infected with a lethal dose of SARS-CoV displayed less weight loss, lower lung viral titer, and reduced lung pathology following prophylactic or therapeutic administration of remdesivir [<xref rid="bib0085" ref-type="bibr">17<sup>••</sup></xref>]. A partial resistance phenotype was attributed to two mutations in the viral RdRp, suggesting remdesivir acts on this target [<xref rid="bib0160" ref-type="bibr">32<sup>••</sup></xref>]. Importantly, the fitness and virulence of remdesivir-resistant SARS-CoV was reduced compared to WT SARS-CoV, indicating the barrier to remdesivir resistance is high [<xref rid="bib0085" ref-type="bibr">17<sup>••</sup></xref>]. Increased potency of remdesivir against CoV lacking ExoN catalytic activity suggests that the drug is sensitive to proofreading by ExoN, albeit to a markedly lower extent than other NIs [<xref rid="bib0160" ref-type="bibr">32<sup>••</sup></xref>]. This raises important questions about the mechanism of CoV inhibition by remdesivir, which may be recognized by ExoN but removed less efficiently or may be less visible to ExoN compared with other NIs. Studies probing the interactions between remdesivir and the CoV replication machinery will likely yield crucial insights into how this NI circumvents or overcomes CoV proofreading activity, which can in turn be applied to modeling the development of new NIs and enhancing potency of existing NIs.</p><p id="par0105"><underline>Beta-</underline><sc>d</sc><underline>-N4-hydroxycytidine (NHC):</underline> NHC is a cytidine analogue that has demonstrated potent, broad-spectrum antiviral activity against Venezuelan equine encephalitis virus (VEEV), respiratory syncytial virus (RSV), influenza A virus (IAV), influenza B virus (IBV), chikungunya virus (CHIKV), and CoVs (<xref rid="tbl0005" ref-type="table">Table 1</xref>). NHC exerts its antiviral effect primarily through mutagenesis of viral RNA [<xref rid="bib0110" ref-type="bibr">22</xref>,<xref rid="bib0165" ref-type="bibr">33</xref>,<xref rid="bib0170" ref-type="bibr">34</xref>,<xref rid="bib0175" ref-type="bibr">35<sup>•</sup></xref>,<xref rid="bib0180" ref-type="bibr">36</xref>]. Serial passaging in the presence of NHC led to low level resistance for VEEV but not RSV, IAV, and bovine viral diarrhea virus, thus indicating a high resistance barrier [<xref rid="bib0165" ref-type="bibr">33</xref>,<xref rid="bib0175" ref-type="bibr">35<sup>•</sup></xref>,<xref rid="bib0185" ref-type="bibr">37</xref>]. Potent anti-CoV activity of NHC was demonstrated for SARS-CoV and HCoV-NL63 [<xref rid="bib0180" ref-type="bibr">36</xref>,<xref rid="bib0190" ref-type="bibr">38</xref>]. Although the mechanism of CoV inhibition has not been determined, micromolar-range EC<sub>50</sub>s suggests that like remdesivir, NHC may also have a novel way of interacting with the CoV replicase. The potent, broad-spectrum antiviral activity exhibited by NHC warrants further investigation into use of NHC for the treatment of CoV infections, either alone or in combination with other DAAs and immunomodulators.</p><p id="par0110"><underline>Other NIs</underline> with <italic>in vitro</italic> activity against CoVs and low cytotoxicity include the adenosine analogue BCX4430, which has broad spectrum activity against positive and negative sense RNA viruses and has shown antiviral activity against MERS-CoV and SARS-CoV [<xref rid="bib0155" ref-type="bibr">31</xref>,<xref rid="bib0195" ref-type="bibr">39</xref>]; the deoxycytidine analogue gemcitabine hydrochloride, a chemotherapy drug that inhibits SARS-CoV and MERS-CoV [<xref rid="bib0200" ref-type="bibr">40</xref>]; the uridine analogue 6-azauridine with activity against HCoV-NL63 [<xref rid="bib0180" ref-type="bibr">36</xref>]; and the immunosuppressant imidazole nucleoside mizoribine which inhibits SARS-CoV (<xref rid="tbl0005" ref-type="table">Table 1</xref>) [<xref rid="bib0090" ref-type="bibr">18</xref>]. Flex-base modification of the guanosine analog acyclovir (acyclovir fleximer) yielded activity against HCoV-NL63 and MERS-CoV (<xref rid="tbl0005" ref-type="table">Table 1</xref>) [<xref rid="bib0205" ref-type="bibr">41</xref>]. More research into the efficacy, potency, and mechanism of CoV inhibition is necessary to determine whether further development of these compounds as CoV antivirals is warranted.</p></sec><sec id="sec0020"><title>Conclusions and outlook</title><p id="par0115">As with SARS-CoV and MERS-CoV, new zoonotic CoVs likely will emerge from divergent virus pools in animal reservoirs. It is therefore critical to develop broad-spectrum anti-CoV strategies aimed at multiple conserved targets and functions. Despite high conservation of the viral RdRp and low tolerance for mutations at key residues, resistance against NIs due to mutations in the viral RdRp has been observed in CoVs and other RNA viruses [<xref rid="bib0160" ref-type="bibr">32<sup>••</sup></xref>,<xref rid="bib0210" ref-type="bibr">42</xref>,<xref rid="bib0215" ref-type="bibr">43<sup>•</sup></xref>,<xref rid="bib0220" ref-type="bibr">44</xref>,<xref rid="bib0225" ref-type="bibr">45</xref>]. Treatment with combinations of potent anti-CoV NIs could increase the barrier to resistance and enhance efficacy, especially if additive or synergistic interactions occur. Moreover, a therapeutic regimen that combines drugs with distinct modes of action or which interfere at different steps in the viral replication cycle could simultaneously increase antiviral potency, broaden the activity spectrum, and reduce the emergence of drug resistance against CoVs. Classes of candidate companion compounds include NIs, helicase inhibitors, protease inhibitors, monoclonal antibodies, viral entry inhibitors, and DEDDh family exoribonuclease inhibitors with potential activity against ExoN [<xref rid="bib0230" ref-type="bibr">46</xref>,<xref rid="bib0235" ref-type="bibr">47<sup>•</sup></xref>,<xref rid="bib0240" ref-type="bibr">48</xref>], the latter deserving special interest. DEDDh inhibitors aurintricarboxylic acid and pontacyl violet 6R effectively inhibited Lassa virus NP exonuclease in a proof-of-concept biochemical assay [<xref rid="bib0240" ref-type="bibr">48</xref>]. The structural and functional conservation across CoV family members and the absence of redundant functions elsewhere in the genome makes ExoN a potential Achilles’ heel. Combining compounds that inhibit ExoN activity with one or more NIs would simultaneously reduce CoV replication fidelity, boost the potency of the NI, mitigate selective pressures leading to drug resistance, and ultimately attenuate viral disease.</p><p id="par0120">Finally, both SARS-CoV and MERS-CoV infections spur exuberant host inflammatory responses that rapidly progress toward severe immunopathology, the most probable driver of morbidity and death rather than direct viral damage to pulmonary tissues [<xref rid="bib0245" ref-type="bibr">49</xref>]. This potentially limits the therapeutic window for DAAs. Thus, combinations of DAAs and targeted immunomodulators may be necessary to halt lethal progression of immunopathology and extend the therapeutic window for intervention. A multicenter, placebo-controlled, double-blind randomized trial (MIRACLE: <ext-link ext-link-type="ClinicalTrials.gov" xlink:href="NCT02845843" id="intr0020">NCT02845843</ext-link>) is currently in progress to determine the efficacy of combining the immunomodulator IFNβ1b with lopinavir-ritonavir, a protease inhibitor cocktail used to treat HIV that also inhibits MERS-CoV <italic>in vitro</italic> [<xref rid="bib0250" ref-type="bibr">50</xref>]. Adequately controlled prospective studies like MIRACLE are urgently needed to assess efficacy of candidate CoV drugs. These studies should include compounds that have demonstrated broad-spectrum <italic>in vivo</italic> efficacy against CoVs, such as remdesivir, knowing that additional novel zoonotic CoVs are an inevitable future occurrence.</p></sec><sec id="sec0025"><title>Conflict of interest statement</title><p id="par0125">Nothing declared.</p></sec><sec id="sec0030"><title>References and recommended reading</title><p id="par0130">Papers of particular interest, published within the period of review, have been highlighted as:<list list-type="simple" id="lis0010"><list-item id="lsti0030"><p id="par0135">• of special interest</p></list-item><list-item id="lsti0035"><p id="par0140">•• of outstanding interest</p></list-item></list></p></sec></body><back><ref-list id="bibl0005"><title>References</title><ref id="bib0005"><label>1</label><element-citation publication-type="journal" id="sbref0005"><person-group person-group-type="author"><name><surname>Su</surname><given-names>S.</given-names></name><name><surname>Wong</surname><given-names>G.</given-names></name><name><surname>Shi</surname><given-names>W.</given-names></name><name><surname>Liu</surname><given-names>J.</given-names></name><name><surname>Lai</surname><given-names>A.C.K.</given-names></name><name><surname>Zhou</surname><given-names>J.</given-names></name><name><surname>Liu</surname><given-names>W.</given-names></name><name><surname>Bi</surname><given-names>Y.</given-names></name><name><surname>Gao</surname><given-names>G.F.</given-names></name></person-group><article-title>Epidemiology, genetic recombination, and pathogenesis of coronaviruses</article-title><source>Trends Microbiol</source><volume>24</volume><year>2016</year><fpage>490</fpage><lpage>502</lpage><pub-id pub-id-type="pmid">27012512</pub-id></element-citation></ref><ref id="bib0010"><label>2</label><mixed-citation publication-type="other" id="oref0010"><bold>Revised U.S. Surveillance Case Definition for Severe Acute Respiratory Syndrome (SARS) and Update on SARS Cases — United States and Worldwide, December 2003.</bold> [date unknown].</mixed-citation></ref><ref id="bib0015"><label>3</label><mixed-citation publication-type="other" id="oref0015"><bold>WHO | Middle East respiratory syndrome coronavirus (MERS-CoV).</bold><italic>WHO</italic> [date unknown.</mixed-citation></ref><ref id="bib0020"><label>4</label><element-citation publication-type="journal" id="sbref0020"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>Y.M.</given-names></name><name><surname>Balkhy</surname><given-names>H.H.</given-names></name><name><surname>Hayden</surname><given-names>F.G.</given-names></name><name><surname>Bouchama</surname><given-names>A.</given-names></name><name><surname>Luke</surname><given-names>T.</given-names></name><name><surname>Baillie</surname><given-names>J.K.</given-names></name><name><surname>Al-Omari</surname><given-names>A.</given-names></name><name><surname>Hajeer</surname><given-names>A.H.</given-names></name><name><surname>Senga</surname><given-names>M.</given-names></name><name><surname>Denison</surname><given-names>M.R.</given-names></name></person-group><article-title>Middle east respiratory syndrome</article-title><source>N Engl J Med</source><volume>376</volume><year>2017</year><fpage>584</fpage><lpage>594</lpage><pub-id pub-id-type="pmid">28177862</pub-id></element-citation></ref><ref id="bib0025"><label>5</label><element-citation publication-type="journal" id="sbref0025"><person-group person-group-type="author"><name><surname>Luo</surname><given-names>C.-M.</given-names></name><name><surname>Wang</surname><given-names>N.</given-names></name><name><surname>Yang</surname><given-names>X.-L.</given-names></name><name><surname>Liu</surname><given-names>H.-Z.</given-names></name><name><surname>Zhang</surname><given-names>W.</given-names></name><name><surname>Li</surname><given-names>B.</given-names></name><name><surname>Hu</surname><given-names>B.</given-names></name><name><surname>Peng</surname><given-names>C.</given-names></name><name><surname>Geng</surname><given-names>Q.-B.</given-names></name><name><surname>Zhu</surname><given-names>G.-J.</given-names></name></person-group><article-title>Discovery of novel bat coronaviruses in South China that use the same receptor as middle east respiratory syndrome coronavirus</article-title><source>J Virol</source><volume>92</volume><year>2018</year></element-citation></ref><ref id="bib0030"><label>6</label><element-citation publication-type="journal" id="sbref0030"><person-group person-group-type="author"><name><surname>Chu</surname><given-names>H.</given-names></name><name><surname>Chan</surname><given-names>C.-M.</given-names></name><name><surname>Zhang</surname><given-names>X.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Yuan</surname><given-names>S.</given-names></name><name><surname>Zhou</surname><given-names>J.</given-names></name><name><surname>Au-Yeung</surname><given-names>R.K.-H.</given-names></name><name><surname>Sze</surname><given-names>K.-H.</given-names></name><name><surname>Yang</surname><given-names>D.</given-names></name><name><surname>Shuai</surname><given-names>H.</given-names></name></person-group><article-title>Middle east respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells</article-title><source>J Biol Chem</source><volume>293</volume><year>2018</year><fpage>11709</fpage><lpage>11726</lpage><pub-id pub-id-type="pmid">29887526</pub-id></element-citation></ref><ref id="bib0035"><label>7</label><element-citation publication-type="journal" id="sbref0035"><person-group person-group-type="author"><name><surname>Modjarrad</surname><given-names>K.</given-names></name><name><surname>Moorthy</surname><given-names>V.S.</given-names></name><name><surname>Ben Embarek</surname><given-names>P.</given-names></name><name><surname>Van Kerkhove</surname><given-names>M.</given-names></name><name><surname>Kim</surname><given-names>J.</given-names></name><name><surname>Kieny</surname><given-names>M.-P.</given-names></name></person-group><article-title>A roadmap for MERS-CoV research and product development: report from a world health organization consultation</article-title><source>Nat Med</source><volume>22</volume><year>2016</year><fpage>701</fpage><lpage>705</lpage><pub-id pub-id-type="pmid">27387881</pub-id></element-citation></ref><ref id="bib0040"><label>8</label><element-citation publication-type="journal" id="sbref0040"><person-group person-group-type="author"><name><surname>Brende</surname><given-names>B.</given-names></name><name><surname>Farrar</surname><given-names>J.</given-names></name><name><surname>Gashumba</surname><given-names>D.</given-names></name><name><surname>Moedas</surname><given-names>C.</given-names></name><name><surname>Mundel</surname><given-names>T.</given-names></name><name><surname>Shiozaki</surname><given-names>Y.</given-names></name><name><surname>Vardhan</surname><given-names>H.</given-names></name><name><surname>Wanka</surname><given-names>J.</given-names></name><name><surname>Røttingen</surname><given-names>J.-A.</given-names></name></person-group><article-title>CEPI-a new global R&D organisation for epidemic preparedness and response</article-title><source>Lancet Lond Engl</source><volume>389</volume><year>2017</year><fpage>233</fpage><lpage>235</lpage></element-citation></ref><ref id="bib0045"><label>9</label><element-citation publication-type="journal" id="sbref0045"><person-group person-group-type="author"><name><surname>Mehand</surname><given-names>M.S.</given-names></name><name><surname>Al-Shorbaji</surname><given-names>F.</given-names></name><name><surname>Millett</surname><given-names>P.</given-names></name><name><surname>Murgue</surname><given-names>B.</given-names></name></person-group><article-title>The WHO R&D blueprint: 2018 review of emerging infectious diseases requiring urgent research and development efforts</article-title><source>Antiviral Res</source><year>2018</year><fpage>63</fpage><lpage>67</lpage></element-citation></ref><ref id="bib0050"><label>10</label><element-citation publication-type="journal" id="sbref0050"><person-group person-group-type="author"><name><surname>Perales</surname><given-names>C.</given-names></name><name><surname>Domingo</surname><given-names>E.</given-names></name></person-group><article-title>Antiviral strategies based on lethal mutagenesis and error threshold</article-title><source>Curr Top Microbiol Immunol</source><volume>392</volume><year>2016</year><fpage>323</fpage><lpage>339</lpage><pub-id pub-id-type="pmid">26294225</pub-id></element-citation></ref><ref id="bib0055"><label>11</label><element-citation publication-type="journal" id="sbref0055"><person-group person-group-type="author"><name><surname>Eckerle</surname><given-names>L.D.</given-names></name><name><surname>Lu</surname><given-names>X.</given-names></name><name><surname>Sperry</surname><given-names>S.M.</given-names></name><name><surname>Choi</surname><given-names>L.</given-names></name><name><surname>Denison</surname><given-names>M.R.</given-names></name></person-group><article-title>High fidelity of murine hepatitis virus replication is decreased in nsp14 exoribonuclease mutants</article-title><source>J Virol</source><volume>81</volume><year>2007</year><fpage>12135</fpage><lpage>12144</lpage><pub-id pub-id-type="pmid">17804504</pub-id></element-citation></ref><ref id="bib0060"><label>12</label><element-citation publication-type="journal" id="sbref0060"><person-group person-group-type="author"><name><surname>Smith</surname><given-names>E.C.</given-names></name><name><surname>Blanc</surname><given-names>H.</given-names></name><name><surname>Vignuzzi</surname><given-names>M.</given-names></name><name><surname>Denison</surname><given-names>M.R.</given-names></name></person-group><article-title>Coronaviruses lacking exoribonuclease activity are susceptible to lethal mutagenesis: evidence for proofreading and potential therapeutics</article-title><source>PLoS Pathog</source><volume>9</volume><year>2013</year><object-id pub-id-type="publisher-id">e1003565</object-id></element-citation></ref><ref id="bib0065"><label>13</label><element-citation publication-type="journal" id="sbref0065"><person-group person-group-type="author"><name><surname>Ferron</surname><given-names>F.</given-names></name><name><surname>Subissi</surname><given-names>L.</given-names></name><name><surname>Silveira De Morais</surname><given-names>A.T.</given-names></name><name><surname>Le</surname><given-names>N.T.T.</given-names></name><name><surname>Sevajol</surname><given-names>M.</given-names></name><name><surname>Gluais</surname><given-names>L.</given-names></name><name><surname>Decroly</surname><given-names>E.</given-names></name><name><surname>Vonrhein</surname><given-names>C.</given-names></name><name><surname>Bricogne</surname><given-names>G.</given-names></name><name><surname>Canard</surname><given-names>B.</given-names></name></person-group><article-title>Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA</article-title><source>Proc Natl Acad Sci U S A</source><volume>115</volume><year>2018</year><fpage>E162</fpage><lpage>E171</lpage><pub-id pub-id-type="pmid">29279395</pub-id></element-citation></ref><ref id="bib0070"><label>14</label><element-citation publication-type="book" id="sbref0070"><person-group person-group-type="author"><name><surname>Tejero</surname><given-names>H.</given-names></name><name><surname>Montero</surname><given-names>F.</given-names></name><name><surname>Nuño</surname><given-names>J.C.</given-names></name></person-group><chapter-title>Theories of lethal mutagenesis: from error catastrophe to lethal defection</chapter-title><person-group person-group-type="editor"><name><surname>Domingo</surname><given-names>E.</given-names></name><name><surname>Schuster</surname><given-names>P.</given-names></name></person-group><source>Quasispecies: From Theory to Experimental Systems</source><year>2016</year><publisher-name>Springer International Publishing</publisher-name><fpage>161</fpage><lpage>179</lpage></element-citation></ref><ref id="bib0075"><label>15</label><element-citation publication-type="journal" id="sbref0075"><person-group person-group-type="author"><name><surname>Te</surname><given-names>H.S.</given-names></name><name><surname>Randall</surname><given-names>G.</given-names></name><name><surname>Jensen</surname><given-names>D.M.</given-names></name></person-group><article-title>Mechanism of action of ribavirin in the treatment of chronic hepatitis C</article-title><source>Gastroenterol Hepatol</source><volume>3</volume><year>2007</year><fpage>218</fpage><lpage>225</lpage></element-citation></ref><ref id="bib0080"><label>16</label><element-citation publication-type="journal" id="sbref0080"><person-group person-group-type="author"><name><surname>Jordan</surname><given-names>P.C.</given-names></name><name><surname>Stevens</surname><given-names>S.K.</given-names></name><name><surname>Deval</surname><given-names>J.</given-names></name></person-group><article-title>Nucleosides for the treatment of respiratory RNA virus infections</article-title><source>Antivir Chem Chemother</source><volume>26</volume><year>2018</year><object-id pub-id-type="publisher-id">2040206618764483</object-id></element-citation></ref><ref id="bib0085"><label>17••</label><element-citation publication-type="journal" id="sbref0085"><person-group person-group-type="author"><name><surname>Sheahan</surname><given-names>T.P.</given-names></name><name><surname>Sims</surname><given-names>A.C.</given-names></name><name><surname>Graham</surname><given-names>R.L.</given-names></name><name><surname>Menachery</surname><given-names>V.D.</given-names></name><name><surname>Gralinski</surname><given-names>L.E.</given-names></name><name><surname>Case</surname><given-names>J.B.</given-names></name><name><surname>Leist</surname><given-names>S.R.</given-names></name><name><surname>Pyrc</surname><given-names>K.</given-names></name><name><surname>Feng</surname><given-names>J.Y.</given-names></name><name><surname>Trantcheva</surname><given-names>I.</given-names></name></person-group><article-title>Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses</article-title><source>Sci Transl Med</source><volume>9</volume><year>2017</year><object-id pub-id-type="publisher-id">eaal3653</object-id></element-citation><note><p>Although nucleoside analogs have been shown effective against many RNA viruses, many do not potently inhibit CoVs. This study demonstrates potent activity of nucleoside analogue GS-5734 against a diverse spectrum of human and zoonotic CoV in human airway epithelial cultures and in mouse models of SARS-CoV and MERS-CoV disease. This is the first study to demonstrate activity of GS-5734 against CoVs.</p></note></ref><ref id="bib0090"><label>18</label><element-citation publication-type="journal" id="sbref0090"><person-group person-group-type="author"><name><surname>Saijo</surname><given-names>M.</given-names></name><name><surname>Morikawa</surname><given-names>S.</given-names></name><name><surname>Fukushi</surname><given-names>S.</given-names></name><name><surname>Mizutani</surname><given-names>T.</given-names></name><name><surname>Hasegawa</surname><given-names>H.</given-names></name><name><surname>Nagata</surname><given-names>N.</given-names></name><name><surname>Iwata</surname><given-names>N.</given-names></name><name><surname>Kurane</surname><given-names>I.</given-names></name></person-group><article-title>Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus</article-title><source>Antiviral Res</source><volume>66</volume><year>2005</year><fpage>159</fpage><lpage>163</lpage><pub-id pub-id-type="pmid">15911031</pub-id></element-citation></ref><ref id="bib0095"><label>19</label><element-citation publication-type="journal" id="sbref0095"><person-group person-group-type="author"><name><surname>Feld</surname><given-names>J.J.</given-names></name><name><surname>Hoofnagle</surname><given-names>J.H.</given-names></name></person-group><article-title>Mechanism of action of interferon and ribavirin in treatment of hepatitis C</article-title><source>Nature</source><volume>436</volume><year>2005</year><fpage>967</fpage><lpage>972</lpage><pub-id pub-id-type="pmid">16107837</pub-id></element-citation></ref><ref id="bib0100"><label>20</label><element-citation publication-type="journal" id="sbref0100"><person-group person-group-type="author"><name><surname>Cameron</surname><given-names>C.E.</given-names></name><name><surname>Castro</surname><given-names>C.</given-names></name></person-group><article-title>The mechanism of action of ribavirin: lethal mutagenesis of RNA virus genomes mediated by the viral RNA-dependent RNA polymerase</article-title><source>Curr Opin Infect Dis</source><volume>14</volume><year>2001</year><fpage>757</fpage><lpage>764</lpage><pub-id pub-id-type="pmid">11964896</pub-id></element-citation></ref><ref id="bib0105"><label>21</label><element-citation publication-type="journal" id="sbref0105"><person-group person-group-type="author"><name><surname>Chan</surname><given-names>J.F.W.</given-names></name><name><surname>Chan</surname><given-names>K.-H.</given-names></name><name><surname>Kao</surname><given-names>R.Y.T.</given-names></name><name><surname>To</surname><given-names>K.K.W.</given-names></name><name><surname>Zheng</surname><given-names>B.-J.</given-names></name><name><surname>Li</surname><given-names>C.P.Y.</given-names></name><name><surname>Li</surname><given-names>P.T.W.</given-names></name><name><surname>Dai</surname><given-names>J.</given-names></name><name><surname>Mok</surname><given-names>F.K.Y.</given-names></name><name><surname>Chen</surname><given-names>H.</given-names></name></person-group><article-title>Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus</article-title><source>J Infect</source><volume>67</volume><year>2013</year><fpage>606</fpage><lpage>616</lpage><pub-id pub-id-type="pmid">24096239</pub-id></element-citation></ref><ref id="bib0110"><label>22</label><element-citation publication-type="journal" id="sbref0110"><person-group person-group-type="author"><name><surname>Barnard</surname><given-names>D.L.</given-names></name><name><surname>Day</surname><given-names>C.W.</given-names></name><name><surname>Bailey</surname><given-names>K.</given-names></name><name><surname>Heiner</surname><given-names>M.</given-names></name><name><surname>Montgomery</surname><given-names>R.</given-names></name><name><surname>Lauridsen</surname><given-names>L.</given-names></name><name><surname>Winslow</surname><given-names>S.</given-names></name><name><surname>Hoopes</surname><given-names>J.</given-names></name><name><surname>JK-K</surname><given-names>Li</given-names></name><name><surname>Lee</surname><given-names>J.</given-names></name></person-group><article-title>Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin</article-title><source>Antiviral Res</source><volume>71</volume><year>2006</year><fpage>53</fpage><lpage>63</lpage><pub-id pub-id-type="pmid">16621037</pub-id></element-citation></ref><ref id="bib0115"><label>23</label><element-citation publication-type="journal" id="sbref0115"><person-group person-group-type="author"><name><surname>Booth</surname><given-names>C.M.</given-names></name><name><surname>Matukas</surname><given-names>L.M.</given-names></name><name><surname>Tomlinson</surname><given-names>G.A.</given-names></name><name><surname>Rachlis</surname><given-names>A.R.</given-names></name><name><surname>Rose</surname><given-names>D.B.</given-names></name><name><surname>Dwosh</surname><given-names>H.A.</given-names></name><name><surname>Walmsley</surname><given-names>S.L.</given-names></name><name><surname>Mazzulli</surname><given-names>T.</given-names></name><name><surname>Avendano</surname><given-names>M.</given-names></name><name><surname>Derkach</surname><given-names>P.</given-names></name></person-group><article-title>Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area</article-title><source>JAMA</source><volume>289</volume><year>2003</year><fpage>2801</fpage><lpage>2809</lpage><pub-id pub-id-type="pmid">12734147</pub-id></element-citation></ref><ref id="bib0120"><label>24</label><element-citation publication-type="journal" id="sbref0120"><person-group person-group-type="author"><name><surname>Gross</surname><given-names>A.E.</given-names></name><name><surname>Bryson</surname><given-names>M.L.</given-names></name></person-group><article-title>Oral Ribavirin for the treatment of noninfluenza respiratory viral infections: a systematic review</article-title><source>Ann Pharmacother</source><volume>49</volume><year>2015</year><fpage>1125</fpage><lpage>1135</lpage><pub-id pub-id-type="pmid">26228937</pub-id></element-citation></ref><ref id="bib0125"><label>25</label><element-citation publication-type="journal" id="sbref0125"><person-group person-group-type="author"><name><surname>Falzarano</surname><given-names>D.</given-names></name><name><surname>de Wit</surname><given-names>E.</given-names></name><name><surname>Rasmussen</surname><given-names>A.L.</given-names></name><name><surname>Feldmann</surname><given-names>F.</given-names></name><name><surname>Okumura</surname><given-names>A.</given-names></name><name><surname>Scott</surname><given-names>D.P.</given-names></name><name><surname>Brining</surname><given-names>D.</given-names></name><name><surname>Bushmaker</surname><given-names>T.</given-names></name><name><surname>Martellaro</surname><given-names>C.</given-names></name><name><surname>Baseler</surname><given-names>L.</given-names></name></person-group><article-title>Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques</article-title><source>Nat Med</source><volume>19</volume><year>2013</year><fpage>1313</fpage><lpage>1317</lpage><pub-id pub-id-type="pmid">24013700</pub-id></element-citation></ref><ref id="bib0130"><label>26</label><element-citation publication-type="journal" id="sbref0130"><person-group person-group-type="author"><name><surname>Falzarano</surname><given-names>D.</given-names></name><name><surname>de Wit</surname><given-names>E.</given-names></name><name><surname>Martellaro</surname><given-names>C.</given-names></name><name><surname>Callison</surname><given-names>J.</given-names></name><name><surname>Munster</surname><given-names>V.J.</given-names></name><name><surname>Feldmann</surname><given-names>H.</given-names></name></person-group><article-title>Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin</article-title><source>Sci Rep</source><volume>3</volume><year>2013</year><object-id pub-id-type="publisher-id">1686</object-id></element-citation></ref><ref id="bib0135"><label>27</label><element-citation publication-type="journal" id="sbref0135"><person-group person-group-type="author"><name><surname>Al-Tawfiq</surname><given-names>J.A.</given-names></name><name><surname>Momattin</surname><given-names>H.</given-names></name><name><surname>Dib</surname><given-names>J.</given-names></name><name><surname>Memish</surname><given-names>Z.A.</given-names></name></person-group><article-title>Ribavirin and interferon therapy in patients infected with the middle east respiratory syndrome coronavirus: an observational study</article-title><source>Int J Infect Dis</source><volume>20</volume><year>2014</year><fpage>42</fpage><lpage>46</lpage><pub-id pub-id-type="pmid">24406736</pub-id></element-citation></ref><ref id="bib0140"><label>28</label><element-citation publication-type="journal" id="sbref0140"><person-group person-group-type="author"><name><surname>Omrani</surname><given-names>A.S.</given-names></name><name><surname>Saad</surname><given-names>M.M.</given-names></name><name><surname>Baig</surname><given-names>K.</given-names></name><name><surname>Bahloul</surname><given-names>A.</given-names></name><name><surname>Abdul-Matin</surname><given-names>M.</given-names></name><name><surname>Alaidaroos</surname><given-names>A.Y.</given-names></name><name><surname>Almakhlafi</surname><given-names>G.A.</given-names></name><name><surname>Albarrak</surname><given-names>M.M.</given-names></name><name><surname>Memish</surname><given-names>Z.A.</given-names></name><name><surname>Albarrak</surname><given-names>A.M.</given-names></name></person-group><article-title>Ribavirin and interferon alfa-2a for severe middle east respiratory syndrome coronavirus infection: a retrospective cohort study</article-title><source>Lancet Infect Dis</source><volume>14</volume><year>2014</year><fpage>1090</fpage><lpage>1095</lpage><pub-id pub-id-type="pmid">25278221</pub-id></element-citation></ref><ref id="bib0145"><label>29</label><element-citation publication-type="journal" id="sbref0145"><person-group person-group-type="author"><name><surname>Shalhoub</surname><given-names>S.</given-names></name><name><surname>Farahat</surname><given-names>F.</given-names></name><name><surname>Al-Jiffri</surname><given-names>A.</given-names></name><name><surname>Simhairi</surname><given-names>R.</given-names></name><name><surname>Shamma</surname><given-names>O.</given-names></name><name><surname>Siddiqi</surname><given-names>N.</given-names></name><name><surname>Mushtaq</surname><given-names>A.</given-names></name></person-group><article-title>IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study</article-title><source>J Antimicrob Chemother</source><volume>70</volume><year>2015</year><fpage>2129</fpage><lpage>2132</lpage><pub-id pub-id-type="pmid">25900158</pub-id></element-citation></ref><ref id="bib0150"><label>30</label><element-citation publication-type="journal" id="sbref0150"><person-group person-group-type="author"><name><surname>Lo</surname><given-names>M.K.</given-names></name><name><surname>Jordan</surname><given-names>R.</given-names></name><name><surname>Arvey</surname><given-names>A.</given-names></name><name><surname>Sudhamsu</surname><given-names>J.</given-names></name><name><surname>Shrivastava-Ranjan</surname><given-names>P.</given-names></name><name><surname>Hotard</surname><given-names>A.L.</given-names></name><name><surname>Flint</surname><given-names>M.</given-names></name><name><surname>McMullan</surname><given-names>L.K.</given-names></name><name><surname>Siegel</surname><given-names>D.</given-names></name><name><surname>Clarke</surname><given-names>M.O.</given-names></name></person-group><article-title>GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses</article-title><source>Sci Rep</source><volume>7</volume><year>2017</year></element-citation></ref><ref id="bib0155"><label>31</label><element-citation publication-type="journal" id="sbref0155"><person-group person-group-type="author"><name><surname>Warren</surname><given-names>T.K.</given-names></name><name><surname>Wells</surname><given-names>J.</given-names></name><name><surname>Panchal</surname><given-names>R.G.</given-names></name><name><surname>Stuthman</surname><given-names>K.S.</given-names></name><name><surname>Garza</surname><given-names>N.L.</given-names></name><name><surname>Van Tongeren</surname><given-names>S.A.</given-names></name><name><surname>Dong</surname><given-names>L.</given-names></name><name><surname>Retterer</surname><given-names>C.J.</given-names></name><name><surname>Eaton</surname><given-names>B.P.</given-names></name><name><surname>Pegoraro</surname><given-names>G.</given-names></name></person-group><article-title>Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430</article-title><source>Nature</source><volume>508</volume><year>2014</year><fpage>402</fpage><lpage>405</lpage><pub-id pub-id-type="pmid">24590073</pub-id></element-citation></ref><ref id="bib0160"><label>32••</label><element-citation publication-type="journal" id="sbref0160"><person-group person-group-type="author"><name><surname>Agostini</surname><given-names>M.L.</given-names></name><name><surname>Andres</surname><given-names>E.L.</given-names></name><name><surname>Sims</surname><given-names>A.C.</given-names></name><name><surname>Graham</surname><given-names>R.L.</given-names></name><name><surname>Sheahan</surname><given-names>T.P.</given-names></name><name><surname>Lu</surname><given-names>X.</given-names></name><name><surname>Smith</surname><given-names>E.C.</given-names></name><name><surname>Case</surname><given-names>J.B.</given-names></name><name><surname>Feng</surname><given-names>J.Y.</given-names></name><name><surname>Jordan</surname><given-names>R.</given-names></name></person-group><article-title>Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease</article-title><source>mBio</source><volume>9</volume><year>2018</year><object-id pub-id-type="publisher-id">e00221-18</object-id></element-citation><note><p>Low level resistance against the potent, broad-spectrum anti-CoV nucleoside analog GS-5734 (remdesivir) was selected by serial passage and is associated with two mutations in the viral RdRP. Remdesivir resistance decreased fitness of MHV and attenuated pathogenesis of SARS-CoV in a mouse model of SARS-CoV disease, supporting further development of remdesivir as a pan-CoV antiviral and raising important questions about the mechanism by which remdesivir overcomes CoV nsp14-ExoN activity.</p></note></ref><ref id="bib0165"><label>33</label><element-citation publication-type="journal" id="sbref0165"><person-group person-group-type="author"><name><surname>Urakova</surname><given-names>N.</given-names></name><name><surname>Kuznetsova</surname><given-names>V.</given-names></name><name><surname>Crossman</surname><given-names>D.K.</given-names></name><name><surname>Sokratian</surname><given-names>A.</given-names></name><name><surname>Guthrie</surname><given-names>D.B.</given-names></name><name><surname>Kolykhalov</surname><given-names>A.A.</given-names></name><name><surname>Lockwood</surname><given-names>M.A.</given-names></name><name><surname>Natchus</surname><given-names>M.G.</given-names></name><name><surname>Crowley</surname><given-names>M.R.</given-names></name><name><surname>Painter</surname><given-names>G.R.</given-names></name></person-group><article-title>β-<sc>d</sc>-N4-hydroxycytidine is a potent anti-alphavirus compound that induces a high level of mutations in the viral genome</article-title><source>J Virol</source><volume>92</volume><year>2018</year><object-id pub-id-type="publisher-id">e01965-17</object-id></element-citation></ref><ref id="bib0170"><label>34</label><element-citation publication-type="journal" id="sbref0170"><person-group person-group-type="author"><name><surname>Ehteshami</surname><given-names>M.</given-names></name><name><surname>Tao</surname><given-names>S.</given-names></name><name><surname>Zandi</surname><given-names>K.</given-names></name><name><surname>Hsiao</surname><given-names>H.-M.</given-names></name><name><surname>Jiang</surname><given-names>Y.</given-names></name><name><surname>Hammond</surname><given-names>E.</given-names></name><name><surname>Amblard</surname><given-names>F.</given-names></name><name><surname>Russell</surname><given-names>O.O.</given-names></name><name><surname>Merits</surname><given-names>A.</given-names></name><name><surname>Schinazi</surname><given-names>R.F.</given-names></name></person-group><article-title>Characterization of β-<sc>d</sc>-N4-hydroxycytidine as a novel inhibitor of chikungunya virus</article-title><source>Antimicrob Agents Chemother</source><volume>61</volume><year>2017</year></element-citation></ref><ref id="bib0175"><label>35•</label><element-citation publication-type="journal" id="sbref0175"><person-group person-group-type="author"><name><surname>Yoon</surname><given-names>J.-J.</given-names></name><name><surname>Toots</surname><given-names>M.</given-names></name><name><surname>Lee</surname><given-names>S.</given-names></name><name><surname>Lee</surname><given-names>M.-E.</given-names></name><name><surname>Ludeke</surname><given-names>B.</given-names></name><name><surname>Luczo</surname><given-names>J.M.</given-names></name><name><surname>Ganti</surname><given-names>K.</given-names></name><name><surname>Cox</surname><given-names>R.M.</given-names></name><name><surname>Sticher</surname><given-names>Z.M.</given-names></name><name><surname>Edpuganti</surname><given-names>V.</given-names></name></person-group><article-title>Orally efficacious broad-spectrum ribonucleoside analog inhibitor of influenza and respiratory syncytial viruses</article-title><source>Antimicrob Agents Chemother</source><volume>62</volume><year>2018</year><object-id pub-id-type="publisher-id">e00766-18</object-id></element-citation><note><p>This study identifies the modified cytidine ribonucleoside analogue β-<sc>d</sc>-N4-hydroxycytidine as a potent broad-spectrum inhibitor of respiratory viruses including respiratory syncytial virus, influenza B virus, and influenza A viruses of human, avian, and swine origins and has a high resistance barrier. This compound also is a candidate for the treatment of CoV infection.</p></note></ref><ref id="bib0180"><label>36</label><element-citation publication-type="journal" id="sbref0180"><person-group person-group-type="author"><name><surname>Pyrc</surname><given-names>K.</given-names></name><name><surname>Bosch</surname><given-names>B.J.</given-names></name><name><surname>Berkhout</surname><given-names>B.</given-names></name><name><surname>Jebbink</surname><given-names>M.F.</given-names></name><name><surname>Dijkman</surname><given-names>R.</given-names></name><name><surname>Rottier</surname><given-names>P.</given-names></name><name><surname>van der Hoek</surname><given-names>L.</given-names></name></person-group><article-title>Inhibition of human coronavirus NL63 infection at early stages of the replication cycle</article-title><source>Antimicrob Agents Chemother</source><volume>50</volume><year>2006</year><fpage>2000</fpage><lpage>2008</lpage><pub-id pub-id-type="pmid">16723558</pub-id></element-citation></ref><ref id="bib0185"><label>37</label><element-citation publication-type="journal" id="sbref0185"><person-group person-group-type="author"><name><surname>Stuyver</surname><given-names>L.J.</given-names></name><name><surname>Whitaker</surname><given-names>T.</given-names></name><name><surname>McBrayer</surname><given-names>T.R.</given-names></name><name><surname>Hernandez-Santiago</surname><given-names>B.I.</given-names></name><name><surname>Lostia</surname><given-names>S.</given-names></name><name><surname>Tharnish</surname><given-names>P.M.</given-names></name><name><surname>Ramesh</surname><given-names>M.</given-names></name><name><surname>Chu</surname><given-names>C.K.</given-names></name><name><surname>Jordan</surname><given-names>R.</given-names></name><name><surname>Shi</surname><given-names>J.</given-names></name></person-group><article-title>Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture</article-title><source>Antimicrob Agents Chemother</source><volume>47</volume><year>2003</year><fpage>244</fpage><lpage>254</lpage><pub-id pub-id-type="pmid">12499198</pub-id></element-citation></ref><ref id="bib0190"><label>38</label><element-citation publication-type="journal" id="sbref0190"><person-group person-group-type="author"><name><surname>Barnard</surname><given-names>D.L.</given-names></name><name><surname>Hubbard</surname><given-names>V.D.</given-names></name><name><surname>Burton</surname><given-names>J.</given-names></name><name><surname>Smee</surname><given-names>D.F.</given-names></name><name><surname>Morrey</surname><given-names>J.D.</given-names></name><name><surname>Otto</surname><given-names>M.J.</given-names></name><name><surname>Sidwell</surname><given-names>R.W.</given-names></name></person-group><article-title>Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and beta-<sc>d</sc>-N4-hydroxycytidine</article-title><source>Antivir Chem Chemother</source><volume>15</volume><year>2004</year><fpage>15</fpage><lpage>22</lpage><pub-id pub-id-type="pmid">15074711</pub-id></element-citation></ref><ref id="bib0195"><label>39</label><element-citation publication-type="journal" id="sbref0195"><person-group person-group-type="author"><name><surname>Taylor</surname><given-names>R.</given-names></name><name><surname>Kotian</surname><given-names>P.</given-names></name><name><surname>Warren</surname><given-names>T.</given-names></name><name><surname>Panchal</surname><given-names>R.</given-names></name><name><surname>Bavari</surname><given-names>S.</given-names></name><name><surname>Julander</surname><given-names>J.</given-names></name><name><surname>Dobo</surname><given-names>S.</given-names></name><name><surname>Rose</surname><given-names>A.</given-names></name><name><surname>El-Kattan</surname><given-names>Y.</given-names></name><name><surname>Taubenheim</surname><given-names>B.</given-names></name></person-group><article-title>BCX4430 – a broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease</article-title><source>J Infect Public Health</source><volume>9</volume><year>2016</year><fpage>220</fpage><lpage>226</lpage><pub-id pub-id-type="pmid">27095300</pub-id></element-citation></ref><ref id="bib0200"><label>40</label><element-citation publication-type="journal" id="sbref0200"><person-group person-group-type="author"><name><surname>Dyall</surname><given-names>J.</given-names></name><name><surname>Coleman</surname><given-names>C.M.</given-names></name><name><surname>Hart</surname><given-names>B.J.</given-names></name><name><surname>Venkataraman</surname><given-names>T.</given-names></name><name><surname>Holbrook</surname><given-names>M.R.</given-names></name><name><surname>Kindrachuk</surname><given-names>J.</given-names></name><name><surname>Johnson</surname><given-names>R.F.</given-names></name><name><surname>Olinger</surname><given-names>G.G.</given-names></name><name><surname>Jahrling</surname><given-names>P.B.</given-names></name><name><surname>Laidlaw</surname><given-names>M.</given-names></name></person-group><article-title>Repurposing of clinically developed drugs for treatment of middle east respiratory syndrome coronavirus infection</article-title><source>Antimicrob Agents Chemother</source><volume>58</volume><year>2014</year><fpage>4885</fpage><lpage>4893</lpage><pub-id pub-id-type="pmid">24841273</pub-id></element-citation></ref><ref id="bib0205"><label>41</label><element-citation publication-type="journal" id="sbref0205"><person-group person-group-type="author"><name><surname>Peters</surname><given-names>H.L.</given-names></name><name><surname>Jochmans</surname><given-names>D.</given-names></name><name><surname>de Wilde</surname><given-names>A.H.</given-names></name><name><surname>Posthuma</surname><given-names>C.C.</given-names></name><name><surname>Snijder</surname><given-names>E.J.</given-names></name><name><surname>Neyts</surname><given-names>J.</given-names></name><name><surname>Seley-Radtke</surname><given-names>K.L.</given-names></name></person-group><article-title>Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity</article-title><source>Bioorg Med Chem Lett</source><volume>25</volume><year>2015</year><fpage>2923</fpage><lpage>2926</lpage><pub-id pub-id-type="pmid">26048809</pub-id></element-citation></ref><ref id="bib0210"><label>42</label><element-citation publication-type="journal" id="sbref0210"><person-group person-group-type="author"><name><surname>Deval</surname><given-names>J.</given-names></name><name><surname>Fung</surname><given-names>A.</given-names></name><name><surname>Stevens</surname><given-names>S.K.</given-names></name><name><surname>Jordan</surname><given-names>P.C.</given-names></name><name><surname>Gromova</surname><given-names>T.</given-names></name><name><surname>Taylor</surname><given-names>J.S.</given-names></name><name><surname>Hong</surname><given-names>J.</given-names></name><name><surname>Meng</surname><given-names>J.</given-names></name><name><surname>Wang</surname><given-names>G.</given-names></name><name><surname>Dyatkina</surname><given-names>N.</given-names></name></person-group><article-title>Biochemical effect of resistance mutations against synergistic inhibitors of RSV RNA polymerase</article-title><source>PLoS One</source><volume>11</volume><year>2016</year><object-id pub-id-type="publisher-id">e0154097</object-id></element-citation></ref><ref id="bib0215"><label>43•</label><element-citation publication-type="journal" id="sbref0215"><person-group person-group-type="author"><name><surname>Eyer</surname><given-names>L.</given-names></name><name><surname>Kondo</surname><given-names>H.</given-names></name><name><surname>Zouharova</surname><given-names>D.</given-names></name><name><surname>Hirano</surname><given-names>M.</given-names></name><name><surname>Valdés</surname><given-names>J.J.</given-names></name><name><surname>Muto</surname><given-names>M.</given-names></name><name><surname>Kastl</surname><given-names>T.</given-names></name><name><surname>Kobayashi</surname><given-names>S.</given-names></name><name><surname>Haviernik</surname><given-names>J.</given-names></name><name><surname>Igarashi</surname><given-names>M.</given-names></name></person-group><article-title>Escape of tick-borne flavivirus from 2′-C-methylated nucleoside antivirals is mediated by a single conservative mutation in NS5 that has a dramatic effect on viral fitness</article-title><source>J Virol 91</source><year>2017</year><fpage>e01028-17</fpage></element-citation><note><p>This study demonstrates that the nucleoside analog 7-deaza-2′-C-methyladenosine (7-deaza-2′-CMA) demonstrates potent antiviral activity against tick-borne encephalitis virus. Resistance generated by serial passaging in the presence of 7-deaza-2′-CMA was associated with a single mutation in the polymerase and resulted in resistance against a broad spectrum of derivative compounds. This finding highlights the importance combination therapy to reduce the emergence of resistant virus.</p></note></ref><ref id="bib0220"><label>44</label><element-citation publication-type="journal" id="sbref0220"><person-group person-group-type="author"><name><surname>Diphoko</surname><given-names>T.</given-names></name><name><surname>Gaseitsiwe</surname><given-names>S.</given-names></name><name><surname>Kasvosve</surname><given-names>I.</given-names></name><name><surname>Moyo</surname><given-names>S.</given-names></name><name><surname>Okatch</surname><given-names>H.</given-names></name><name><surname>Musonda</surname><given-names>R.</given-names></name><name><surname>Wainberg</surname><given-names>M.</given-names></name><name><surname>Makhema</surname><given-names>J.</given-names></name><name><surname>Marlink</surname><given-names>R.</given-names></name><name><surname>Novitsky</surname><given-names>V.</given-names></name></person-group><article-title>Prevalence of rilpivirine and etravirine resistance mutations in HIV-1 subtype C-infected patients failing nevirapine or efavirenz-based combination antiretroviral therapy in botswana</article-title><source>AIDS Res Hum Retroviruses</source><volume>34</volume><year>2018</year><fpage>667</fpage><lpage>671</lpage><pub-id pub-id-type="pmid">29732907</pub-id></element-citation></ref><ref id="bib0225"><label>45</label><element-citation publication-type="journal" id="sbref0225"><person-group person-group-type="author"><name><surname>Valdés</surname><given-names>J.J.</given-names></name><name><surname>Butterill</surname><given-names>P.T.</given-names></name><name><surname>Růžek</surname><given-names>D.</given-names></name></person-group><article-title>Flaviviridae viruses use a common molecular mechanism to escape nucleoside analogue inhibitors</article-title><source>Biochem Biophys Res Commun</source><volume>492</volume><year>2017</year><fpage>652</fpage><lpage>658</lpage><pub-id pub-id-type="pmid">28322784</pub-id></element-citation></ref><ref id="bib0230"><label>46</label><element-citation publication-type="journal" id="sbref0230"><person-group person-group-type="author"><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></person-group><article-title>Coronaviruses - drug discovery and therapeutic options</article-title><source>Nat Rev Drug Discov</source><volume>15</volume><year>2016</year><fpage>327</fpage><lpage>347</lpage><pub-id pub-id-type="pmid">26868298</pub-id></element-citation></ref><ref id="bib0235"><label>47•</label><element-citation publication-type="journal" id="sbref0235"><person-group person-group-type="author"><name><surname>Liang</surname><given-names>R.</given-names></name><name><surname>Wang</surname><given-names>L.</given-names></name><name><surname>Zhang</surname><given-names>N.</given-names></name><name><surname>Deng</surname><given-names>X.</given-names></name><name><surname>Su</surname><given-names>M.</given-names></name><name><surname>Su</surname><given-names>Y.</given-names></name><name><surname>Hu</surname><given-names>L.</given-names></name><name><surname>He</surname><given-names>C.</given-names></name><name><surname>Ying</surname><given-names>T.</given-names></name><name><surname>Jiang</surname><given-names>S.</given-names></name></person-group><article-title>Development of small-molecule MERS-CoV inhibitors</article-title><source>Viruses</source><volume>10</volume><year>2018</year><fpage>721</fpage></element-citation><note><p>Comprehensive review of small-molecule inhibitors targeting viral proteins at different stages of the MERS-CoV viral replication cycle. Illustrates chemical structure formulas of inhibitors and summarizes potency, cytotoxicity, and testing model of each inhibitor in a table.</p></note></ref><ref id="bib0240"><label>48</label><element-citation publication-type="journal" id="sbref0240"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>K.-W.</given-names></name><name><surname>Hsu</surname><given-names>K.-C.</given-names></name><name><surname>Chu</surname><given-names>L.-Y.</given-names></name><name><surname>Yang</surname><given-names>J.-M.</given-names></name><name><surname>Yuan</surname><given-names>H.S.</given-names></name><name><surname>Hsiao</surname><given-names>Y.-Y.</given-names></name></person-group><article-title>Identification of inhibitors for the DEDDh family of exonucleases and a unique inhibition mechanism by Crystal structure analysis of CRN-4 bound with 2-Morpholin-4-ylethanesulfonate (MES)</article-title><source>J Med Chem</source><volume>59</volume><year>2016</year><fpage>8019</fpage><lpage>8029</lpage><pub-id pub-id-type="pmid">27529560</pub-id></element-citation></ref><ref id="bib0245"><label>49</label><element-citation publication-type="journal" id="sbref0245"><person-group person-group-type="author"><name><surname>Gralinski</surname><given-names>L.E.</given-names></name><name><surname>Baric</surname><given-names>R.S.</given-names></name></person-group><article-title>Molecular pathology of emerging coronavirus infections</article-title><source>J Pathol</source><volume>235</volume><year>2015</year><fpage>185</fpage><lpage>195</lpage><pub-id pub-id-type="pmid">25270030</pub-id></element-citation></ref><ref id="bib0250"><label>50</label><element-citation publication-type="journal" id="sbref0250"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>Y.M.</given-names></name><name><surname>Alothman</surname><given-names>A.</given-names></name><name><surname>Balkhy</surname><given-names>H.H.</given-names></name><name><surname>Al-Dawood</surname><given-names>A.</given-names></name><name><surname>AlJohani</surname><given-names>S.</given-names></name><name><surname>Al Harbi</surname><given-names>S.</given-names></name><name><surname>Kojan</surname><given-names>S.</given-names></name><name><surname>Al Jeraisy</surname><given-names>M.</given-names></name><name><surname>Deeb</surname><given-names>A.M.</given-names></name><name><surname>Assiri</surname><given-names>A.M.</given-names></name></person-group><article-title>Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial</article-title><source>Trials</source><volume>19</volume><year>2018</year><fpage>81</fpage><pub-id pub-id-type="pmid">29382391</pub-id></element-citation></ref><ref id="bib0255"><label>51</label><element-citation publication-type="journal" id="sbref0255"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>F.</given-names></name><name><surname>Chan</surname><given-names>K.H.</given-names></name><name><surname>Jiang</surname><given-names>Y.</given-names></name><name><surname>Kao</surname><given-names>R.Y.T.</given-names></name><name><surname>Lu</surname><given-names>H.T.</given-names></name><name><surname>Fan</surname><given-names>K.W.</given-names></name><name><surname>Cheng</surname><given-names>V.C.C.</given-names></name><name><surname>Tsui</surname><given-names>W.H.W.</given-names></name><name><surname>Hung</surname><given-names>I.F.N.</given-names></name><name><surname>Lee</surname><given-names>T.S.W.</given-names></name></person-group><article-title><italic>In vitro</italic> susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds</article-title><source>J Clin Virol</source><volume>31</volume><year>2004</year><fpage>69</fpage><lpage>75</lpage><pub-id pub-id-type="pmid">15288617</pub-id></element-citation></ref></ref-list><ack id="ack0005"><title>Acknowledgements</title><p>We thank Jim Chappell and Maria Agostini for careful review of this manuscript. This work was supported by the <funding-source id="gs0005">National Institutes of Health</funding-source> [U19 AI109680, R01 AI132178, R01 AI108197].</p></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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