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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses</title><author><name sortKey="Sheahan, Timothy P" sort="Sheahan, Timothy P" uniqKey="Sheahan T" first="Timothy P." last="Sheahan">Timothy P. Sheahan</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. Gralinski</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Case, James B" sort="Case, James B" uniqKey="Case J" first="James B." last="Case">James B. Case</name><affiliation><nlm:aff id="A4">Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN</nlm:aff></affiliation></author><author><name sortKey="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R." last="Leist">Sarah R. Leist</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Pyrc, Krzysztof" sort="Pyrc, Krzysztof" uniqKey="Pyrc K" first="Krzysztof" last="Pyrc">Krzysztof Pyrc</name><affiliation><nlm:aff id="A5">Department of Microbiology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland</nlm:aff></affiliation></author><author><name sortKey="Feng, Joy Y" sort="Feng, Joy Y" uniqKey="Feng J" first="Joy Y." last="Feng">Joy Y. Feng</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Trantcheva, Iva" sort="Trantcheva, Iva" uniqKey="Trantcheva I" first="Iva" last="Trantcheva">Iva Trantcheva</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Bannister, Roy" sort="Bannister, Roy" uniqKey="Bannister R" first="Roy" last="Bannister">Roy Bannister</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Park, Yeojin" sort="Park, Yeojin" uniqKey="Park Y" first="Yeojin" last="Park">Yeojin Park</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Babusis, Darius" sort="Babusis, Darius" uniqKey="Babusis D" first="Darius" last="Babusis">Darius Babusis</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Clarke, Michael O" sort="Clarke, Michael O" uniqKey="Clarke M" first="Michael O." last="Clarke">Michael O. Clarke</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Mackman, Richard L" sort="Mackman, Richard L" uniqKey="Mackman R" first="Richard L." last="Mackman">Richard L. Mackman</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Spahn, Jamie E" sort="Spahn, Jamie E" uniqKey="Spahn J" first="Jamie E." last="Spahn">Jamie E. Spahn</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Palmiotti, Christopher A" sort="Palmiotti, Christopher A" uniqKey="Palmiotti C" first="Christopher A." last="Palmiotti">Christopher A. Palmiotti</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Siegel, Dustin" sort="Siegel, Dustin" uniqKey="Siegel D" first="Dustin" last="Siegel">Dustin Siegel</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Ray, Adrian S" sort="Ray, Adrian S" uniqKey="Ray A" first="Adrian S." last="Ray">Adrian S. Ray</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Jordan, Robert" sort="Jordan, Robert" uniqKey="Jordan R" first="Robert" last="Jordan">Robert Jordan</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</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="A3">Department of Pediatrics-Infectious Diseases, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN</nlm:aff></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28659436</idno><idno type="pmc">5567817</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567817</idno><idno type="RBID">PMC:5567817</idno><idno type="doi">10.1126/scitranslmed.aal3653</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000D31</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000D31</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses</title><author><name sortKey="Sheahan, Timothy P" sort="Sheahan, Timothy P" uniqKey="Sheahan T" first="Timothy P." last="Sheahan">Timothy P. Sheahan</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Sims, Amy C" sort="Sims, Amy C" uniqKey="Sims A" first="Amy C." last="Sims">Amy C. Sims</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L." last="Graham">Rachel L. Graham</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Menachery, Vineet D" sort="Menachery, Vineet D" uniqKey="Menachery V" first="Vineet D." last="Menachery">Vineet D. Menachery</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E." last="Gralinski">Lisa E. Gralinski</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Case, James B" sort="Case, James B" uniqKey="Case J" first="James B." last="Case">James B. Case</name><affiliation><nlm:aff id="A4">Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN</nlm:aff></affiliation></author><author><name sortKey="Leist, Sarah R" sort="Leist, Sarah R" uniqKey="Leist S" first="Sarah R." last="Leist">Sarah R. Leist</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author><author><name sortKey="Pyrc, Krzysztof" sort="Pyrc, Krzysztof" uniqKey="Pyrc K" first="Krzysztof" last="Pyrc">Krzysztof Pyrc</name><affiliation><nlm:aff id="A5">Department of Microbiology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland</nlm:aff></affiliation></author><author><name sortKey="Feng, Joy Y" sort="Feng, Joy Y" uniqKey="Feng J" first="Joy Y." last="Feng">Joy Y. Feng</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Trantcheva, Iva" sort="Trantcheva, Iva" uniqKey="Trantcheva I" first="Iva" last="Trantcheva">Iva Trantcheva</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Bannister, Roy" sort="Bannister, Roy" uniqKey="Bannister R" first="Roy" last="Bannister">Roy Bannister</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Park, Yeojin" sort="Park, Yeojin" uniqKey="Park Y" first="Yeojin" last="Park">Yeojin Park</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Babusis, Darius" sort="Babusis, Darius" uniqKey="Babusis D" first="Darius" last="Babusis">Darius Babusis</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Clarke, Michael O" sort="Clarke, Michael O" uniqKey="Clarke M" first="Michael O." last="Clarke">Michael O. Clarke</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Mackman, Richard L" sort="Mackman, Richard L" uniqKey="Mackman R" first="Richard L." last="Mackman">Richard L. Mackman</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Spahn, Jamie E" sort="Spahn, Jamie E" uniqKey="Spahn J" first="Jamie E." last="Spahn">Jamie E. Spahn</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Palmiotti, Christopher A" sort="Palmiotti, Christopher A" uniqKey="Palmiotti C" first="Christopher A." last="Palmiotti">Christopher A. Palmiotti</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Siegel, Dustin" sort="Siegel, Dustin" uniqKey="Siegel D" first="Dustin" last="Siegel">Dustin Siegel</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Ray, Adrian S" sort="Ray, Adrian S" uniqKey="Ray A" first="Adrian S." last="Ray">Adrian S. Ray</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</nlm:aff></affiliation></author><author><name sortKey="Jordan, Robert" sort="Jordan, Robert" uniqKey="Jordan R" first="Robert" last="Jordan">Robert Jordan</name><affiliation><nlm:aff id="A2">Gilead Sciences, Inc., Foster City, CA</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="A3">Department of Pediatrics-Infectious Diseases, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN</nlm:aff></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S." last="Baric">Ralph S. Baric</name><affiliation><nlm:aff id="A1">Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</nlm:aff></affiliation></author></analytic><series><title level="j">Science translational medicine</title><idno type="ISSN">1946-6234</idno><idno type="eISSN">1946-6242</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Emerging viral infections are difficult to control as heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. SARS-CoV and MERS-CoV successively emerged causing severe epidemic respiratory disease in immunologically naïve human populations throughout the globe. Broad-spectrum therapies capable of inhibiting CoV infections would address an immediate unmet medical need and could be invaluable in the treatment of emerging and endemic CoV infections. Here we show that a nucleotide prodrug GS-5734, currently in clinical development for treatment of Ebola virus disease, can inhibit SARS-CoV and MERS-CoV replication in multiple in vitro systems including primary human airway epithelial cell cultures with submicromolar IC<sub>50</sub> values. GS-5734 was also effective against bat-CoVs, prepandemic bat-CoVs and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory functions. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and possibly most importantly, emerging CoV of the future.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101505086</journal-id><journal-id journal-id-type="pubmed-jr-id">36963</journal-id><journal-id journal-id-type="nlm-ta">Sci Transl Med</journal-id><journal-id journal-id-type="iso-abbrev">Sci Transl Med</journal-id><journal-title-group><journal-title>Science translational medicine</journal-title></journal-title-group><issn pub-type="ppub">1946-6234</issn><issn pub-type="epub">1946-6242</issn></journal-meta><article-meta><article-id pub-id-type="pmid">28659436</article-id><article-id pub-id-type="pmc">5567817</article-id><article-id pub-id-type="doi">10.1126/scitranslmed.aal3653</article-id><article-id pub-id-type="manuscript">NIHMS895143</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sheahan</surname><given-names>Timothy P.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">$</xref></contrib><contrib contrib-type="author"><name><surname>Sims</surname><given-names>Amy C.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">$</xref></contrib><contrib contrib-type="author"><name><surname>Graham</surname><given-names>Rachel L.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Menachery</surname><given-names>Vineet D.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Gralinski</surname><given-names>Lisa E.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Case</surname><given-names>James B.</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Leist</surname><given-names>Sarah R.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Pyrc</surname><given-names>Krzysztof</given-names></name><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Feng</surname><given-names>Joy Y.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Trantcheva</surname><given-names>Iva</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Bannister</surname><given-names>Roy</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Yeojin</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Babusis</surname><given-names>Darius</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Clarke</surname><given-names>Michael O.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Mackman</surname><given-names>Richard L.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Spahn</surname><given-names>Jamie E.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Palmiotti</surname><given-names>Christopher A.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Siegel</surname><given-names>Dustin</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Ray</surname><given-names>Adrian S.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Cihlar</surname><given-names>Tomas</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Jordan</surname><given-names>Robert</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Denison</surname><given-names>Mark R.</given-names></name><xref ref-type="aff" rid="A3">3</xref><xref rid="FN1" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Baric</surname><given-names>Ralph S.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref rid="FN1" ref-type="author-notes">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC</aff><aff id="A2"><label>2</label>Gilead Sciences, Inc., Foster City, CA</aff><aff id="A3"><label>3</label>Department of Pediatrics-Infectious Diseases, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN</aff><aff id="A4"><label>4</label>Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN</aff><aff id="A5"><label>5</label>Department of Microbiology, Faculty of Biochemistry Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland</aff><author-notes><fn id="FN1"><label>*</label><p>Co-corresponding authors</p></fn><fn id="FN2" fn-type="equal"><label>$</label><p>These authors contributed equally to this work</p></fn><fn fn-type="COI-statement" id="FN4"><p><bold>Competing interests:</bold> The authors affiliated with Gilead Sciences are employees of the company and may own company stock. M.O.C., J.Y.F, R.J., R.L.M., A.S.R., and D.S. are listed as inventors on International Application No. PCT/US2016/052092 filed by Gilead Sciences, Inc., directed to methods of treating coronaviridae virus infections. Travel of M.R.D. to Gilead Sciences, Inc. to discuss this project was paid for by Gilead Sciences.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>28</day><month>7</month><year>2017</year></pub-date><pub-date pub-type="ppub"><day>28</day><month>6</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>23</day><month>8</month><year>2017</year></pub-date><volume>9</volume><issue>396</issue><elocation-id>eaal3653</elocation-id><abstract><p id="P1">Emerging viral infections are difficult to control as heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. SARS-CoV and MERS-CoV successively emerged causing severe epidemic respiratory disease in immunologically naïve human populations throughout the globe. Broad-spectrum therapies capable of inhibiting CoV infections would address an immediate unmet medical need and could be invaluable in the treatment of emerging and endemic CoV infections. Here we show that a nucleotide prodrug GS-5734, currently in clinical development for treatment of Ebola virus disease, can inhibit SARS-CoV and MERS-CoV replication in multiple in vitro systems including primary human airway epithelial cell cultures with submicromolar IC<sub>50</sub> values. GS-5734 was also effective against bat-CoVs, prepandemic bat-CoVs and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory functions. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and possibly most importantly, emerging CoV of the future.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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