Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
Identifieur interne : 003178 ( Ncbi/Merge ); précédent : 003177; suivant : 003179Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection
Auteurs : Emmie De Wit ; Friederike Feldmann ; Jacqueline Cronin ; Robert Jordan ; Atsushi Okumura ; Tina Thomas ; Dana Scott ; Tomas Cihlar ; Heinz FeldmannSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2020.
Descripteurs français
- KwdFr :
- AMP (analogues et dérivés), AMP (pharmacologie), Alanine (analogues et dérivés), Alanine (pharmacologie), Animaux, Antiviraux (pharmacologie), Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Infections à coronavirus (), Infections à coronavirus (traitement médicamenteux), Macaca mulatta, Modèles animaux de maladie humaine, Mâle, Pandémies, Pneumopathie virale, Poumon (anatomopathologie), Poumon (virologie), Prophylaxie après exposition, Réplication virale ().
- MESH :
- analogues et dérivés : AMP, Alanine.
- anatomopathologie : Poumon.
- pharmacologie : AMP, Alanine, Antiviraux.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- traitement médicamenteux : Infections à coronavirus.
- virologie : Poumon.
- Animaux, Charge virale, Coronavirus du syndrome respiratoire du Moyen-Orient, Infections à coronavirus, Macaca mulatta, Modèles animaux de maladie humaine, Mâle, Pandémies, Pneumopathie virale, Prophylaxie après exposition, Réplication virale.
English descriptors
- KwdEn :
- Adenosine Monophosphate (analogs & derivatives), Adenosine Monophosphate (pharmacology), Alanine (analogs & derivatives), Alanine (pharmacology), Animals, Antiviral Agents (pharmacology), Betacoronavirus, Coronavirus Infections (drug therapy), Coronavirus Infections (prevention & control), Disease Models, Animal, Lung (pathology), Lung (virology), Macaca mulatta, Male, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (physiology), Pandemics, Pneumonia, Viral, Post-Exposure Prophylaxis, Viral Load, Virus Replication (drug effects).
- MESH :
- chemical , analogs & derivatives : Adenosine Monophosphate, Alanine.
- chemical , pharmacology : Adenosine Monophosphate, Alanine, Antiviral Agents.
- drug effects : Middle East Respiratory Syndrome Coronavirus, Virus Replication.
- drug therapy : Coronavirus Infections.
- pathology : Lung.
- physiology : Middle East Respiratory Syndrome Coronavirus.
- prevention & control : Coronavirus Infections.
- virology : Lung.
- Animals, Betacoronavirus, Disease Models, Animal, Macaca mulatta, Male, Pandemics, Pneumonia, Viral, Post-Exposure Prophylaxis, Viral Load.
Abstract
Middle East Respiratory Syndrome, caused by the MERS coronavirus (MERS-CoV), continues to cause severe respiratory disease with a high case fatality rate. To date, potential antiviral treatments for MERS-CoV have shown limited efficacy in animal studies. Here, we tested the efficacy of the broad-acting antiviral remdesivir in the rhesus macaque model of MERS-CoV infection. Remdesivir reduced the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. It may also have utility for related coronaviruses such as the novel coronavirus 2019-nCoV emerging from Wuhan, China.
Url:
DOI: 10.1073/pnas.1922083117
PubMed: 32054787
PubMed Central: 7104368
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PMC:7104368Le document en format XML
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xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>AMP</term><term>Alanine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>AMP</term><term>Alanine</term><term>Antiviraux</term></keywords><keywords scheme="MESH" 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To date, potential antiviral treatments for MERS-CoV have shown limited efficacy in animal studies. Here, we tested the efficacy of the broad-acting antiviral remdesivir in the rhesus macaque model of MERS-CoV infection. Remdesivir reduced the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. It may also have utility for related coronaviruses such as the novel coronavirus 2019-nCoV emerging from Wuhan, China.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Modjarrad, K" uniqKey="Modjarrad K">K. Modjarrad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brende, B" uniqKey="Brende B">B. Brende</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lo, M K" uniqKey="Lo M">M. K. Lo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Warren, T K" uniqKey="Warren T">T. K. Warren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lo, M K" uniqKey="Lo M">M. K. Lo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, T P" uniqKey="Sheahan T">T. P. Sheahan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, T P" uniqKey="Sheahan T">T. P. Sheahan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agostini, M L" uniqKey="Agostini M">M. L. Agostini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. de Wit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hui, D S" uniqKey="Hui D">D. S. Hui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A. Assiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, J F" uniqKey="Chan J">J. F. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. de Wit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N. van Doremalen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Abdely, H M" uniqKey="Al Abdely H">H. M. Al-Abdely</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bin, S Y" uniqKey="Bin S">S. Y. Bin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prescott, J" uniqKey="Prescott J">J. Prescott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dornemann, J" uniqKey="Dornemann J">J. Dörnemann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacobs, M" uniqKey="Jacobs M">M. Jacobs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mulangu, S" uniqKey="Mulangu S">S. Mulangu</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brining, D L" uniqKey="Brining D">D. L. Brining</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, V M" uniqKey="Corman V">V. M. Corman</name></author></analytic></biblStruct></listBibl></div1></back></TEI><double pmid="32054787"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection</title><author><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name><affiliation><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</nlm:aff></affiliation></author><author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><affiliation><nlm:aff id="aff2">Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</nlm:aff></affiliation></author><author><name sortKey="Cronin, Jacqueline" sort="Cronin, Jacqueline" uniqKey="Cronin J" first="Jacqueline" last="Cronin">Jacqueline Cronin</name><affiliation><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</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="aff3">Biology Department,<institution>Gilead Sciences</institution>, Foster City,<addr-line>CA</addr-line> 94404;</nlm:aff></affiliation></author><author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><affiliation><nlm:aff id="aff4">Center for Infection and Immunity, Mailman School of Public Health,<institution>Columbia University</institution>, New York,<addr-line>NY</addr-line> 10032</nlm:aff></affiliation></author><author><name sortKey="Thomas, Tina" sort="Thomas, Tina" uniqKey="Thomas T" first="Tina" last="Thomas">Tina Thomas</name><affiliation><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</nlm:aff></affiliation></author><author><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name><affiliation><nlm:aff id="aff2">Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</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="aff3">Biology Department,<institution>Gilead Sciences</institution>, Foster City,<addr-line>CA</addr-line> 94404;</nlm:aff></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32054787</idno><idno type="pmc">7104368</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104368</idno><idno type="RBID">PMC:7104368</idno><idno type="doi">10.1073/pnas.1922083117</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">001440</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001440</idno><idno type="wicri:Area/Pmc/Curation">001440</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001440</idno><idno type="wicri:Area/Pmc/Checkpoint">000128</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000128</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection</title><author><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name><affiliation><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</nlm:aff></affiliation></author><author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><affiliation><nlm:aff id="aff2">Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</nlm:aff></affiliation></author><author><name sortKey="Cronin, Jacqueline" sort="Cronin, Jacqueline" uniqKey="Cronin J" first="Jacqueline" last="Cronin">Jacqueline Cronin</name><affiliation><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</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="aff3">Biology Department,<institution>Gilead Sciences</institution>, Foster City,<addr-line>CA</addr-line> 94404;</nlm:aff></affiliation></author><author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><affiliation><nlm:aff id="aff4">Center for Infection and Immunity, Mailman School of Public Health,<institution>Columbia University</institution>, New York,<addr-line>NY</addr-line> 10032</nlm:aff></affiliation></author><author><name sortKey="Thomas, Tina" sort="Thomas, Tina" uniqKey="Thomas T" first="Tina" last="Thomas">Tina Thomas</name><affiliation><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</nlm:aff></affiliation></author><author><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name><affiliation><nlm:aff id="aff2">Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</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="aff3">Biology Department,<institution>Gilead Sciences</institution>, Foster City,<addr-line>CA</addr-line> 94404;</nlm:aff></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation><nlm:aff id="aff1">Laboratory of Virology, National Institute of Allergy and Infectious Diseases,<institution>NIH</institution>, Hamilton,<addr-line>MT</addr-line> 59840;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Middle East Respiratory Syndrome, caused by the MERS coronavirus (MERS-CoV), continues to cause severe respiratory disease with a high case fatality rate. To date, potential antiviral treatments for MERS-CoV have shown limited efficacy in animal studies. Here, we tested the efficacy of the broad-acting antiviral remdesivir in the rhesus macaque model of MERS-CoV infection. Remdesivir reduced the severity of disease, virus replication, and damage to the lungs when administered either before or after animals were infected with MERS-CoV. Our data show that remdesivir is a promising antiviral treatment against MERS that could be considered for implementation in clinical trials. It may also have utility for related coronaviruses such as the novel coronavirus 2019-nCoV emerging from Wuhan, China.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Modjarrad, K" uniqKey="Modjarrad K">K. Modjarrad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brende, B" uniqKey="Brende B">B. Brende</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lo, M K" uniqKey="Lo M">M. K. Lo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Warren, T K" uniqKey="Warren T">T. K. Warren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lo, M K" uniqKey="Lo M">M. K. Lo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, T P" uniqKey="Sheahan T">T. P. Sheahan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, T P" uniqKey="Sheahan T">T. P. Sheahan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agostini, M L" uniqKey="Agostini M">M. L. Agostini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. de Wit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hui, D S" uniqKey="Hui D">D. S. Hui</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A. Assiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, J F" uniqKey="Chan J">J. F. Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. de Wit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N. van Doremalen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Abdely, H M" uniqKey="Al Abdely H">H. M. Al-Abdely</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bin, S Y" uniqKey="Bin S">S. Y. Bin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prescott, J" uniqKey="Prescott J">J. Prescott</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dornemann, J" uniqKey="Dornemann J">J. Dörnemann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jacobs, M" uniqKey="Jacobs M">M. Jacobs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mulangu, S" uniqKey="Mulangu S">S. Mulangu</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brining, D L" uniqKey="Brining D">D. L. Brining</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, V M" uniqKey="Corman V">V. M. Corman</name></author></analytic></biblStruct></listBibl></div1></back></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.</title><author><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840; Emmie.deWit@nih.gov.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><affiliation wicri:level="2"><nlm:affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Cronin, Jacqueline" sort="Cronin, Jacqueline" uniqKey="Cronin J" first="Jacqueline" last="Cronin">Jacqueline Cronin</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Jordan, Robert" sort="Jordan, Robert" uniqKey="Jordan R" first="Robert" last="Jordan">Robert Jordan</name><affiliation wicri:level="2"><nlm:affiliation>Biology Department, Gilead Sciences, Foster City, CA 94404.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Biology Department, Gilead Sciences, Foster City</wicri:cityArea></affiliation></author><author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><affiliation wicri:level="2"><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Thomas, Tina" sort="Thomas, Tina" uniqKey="Thomas T" first="Tina" last="Thomas">Tina Thomas</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name><affiliation wicri:level="2"><nlm:affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name><affiliation wicri:level="2"><nlm:affiliation>Biology Department, Gilead Sciences, Foster City, CA 94404.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Biology Department, Gilead Sciences, Foster City</wicri:cityArea></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32054787</idno><idno type="pmid">32054787</idno><idno type="doi">10.1073/pnas.1922083117</idno><idno type="wicri:Area/PubMed/Corpus">000795</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000795</idno><idno type="wicri:Area/PubMed/Curation">000795</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000795</idno><idno type="wicri:Area/PubMed/Checkpoint">000290</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000290</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection.</title><author><name sortKey="De Wit, Emmie" sort="De Wit, Emmie" uniqKey="De Wit E" first="Emmie" last="De Wit">Emmie De Wit</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840; Emmie.deWit@nih.gov.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Feldmann, Friederike" sort="Feldmann, Friederike" uniqKey="Feldmann F" first="Friederike" last="Feldmann">Friederike Feldmann</name><affiliation wicri:level="2"><nlm:affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Cronin, Jacqueline" sort="Cronin, Jacqueline" uniqKey="Cronin J" first="Jacqueline" last="Cronin">Jacqueline Cronin</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Jordan, Robert" sort="Jordan, Robert" uniqKey="Jordan R" first="Robert" last="Jordan">Robert Jordan</name><affiliation wicri:level="2"><nlm:affiliation>Biology Department, Gilead Sciences, Foster City, CA 94404.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Biology Department, Gilead Sciences, Foster City</wicri:cityArea></affiliation></author><author><name sortKey="Okumura, Atsushi" sort="Okumura, Atsushi" uniqKey="Okumura A" first="Atsushi" last="Okumura">Atsushi Okumura</name><affiliation wicri:level="2"><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY 10032.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York</wicri:cityArea></affiliation></author><author><name sortKey="Thomas, Tina" sort="Thomas, Tina" uniqKey="Thomas T" first="Tina" last="Thomas">Tina Thomas</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Scott, Dana" sort="Scott, Dana" uniqKey="Scott D" first="Dana" last="Scott">Dana Scott</name><affiliation wicri:level="2"><nlm:affiliation>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Cihlar, Tomas" sort="Cihlar, Tomas" uniqKey="Cihlar T" first="Tomas" last="Cihlar">Tomas Cihlar</name><affiliation wicri:level="2"><nlm:affiliation>Biology Department, Gilead Sciences, Foster City, CA 94404.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Biology Department, Gilead Sciences, Foster City</wicri:cityArea></affiliation></author><author><name sortKey="Feldmann, Heinz" sort="Feldmann, Heinz" uniqKey="Feldmann H" first="Heinz" last="Feldmann">Heinz Feldmann</name><affiliation wicri:level="2"><nlm:affiliation>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea>Laboratory of Virology, National Institute of Allergy and Infectious Diseases, NIH, Hamilton</wicri:cityArea></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine Monophosphate (analogs & derivatives)</term><term>Adenosine Monophosphate (pharmacology)</term><term>Alanine (analogs & derivatives)</term><term>Alanine (pharmacology)</term><term>Animals</term><term>Antiviral Agents (pharmacology)</term><term>Betacoronavirus</term><term>Coronavirus Infections (drug therapy)</term><term>Coronavirus Infections (prevention & control)</term><term>Disease Models, Animal</term><term>Lung (pathology)</term><term>Lung (virology)</term><term>Macaca mulatta</term><term>Male</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Middle East Respiratory Syndrome Coronavirus (physiology)</term><term>Pandemics</term><term>Pneumonia, Viral</term><term>Post-Exposure Prophylaxis</term><term>Viral Load</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>AMP (analogues et dérivés)</term><term>AMP (pharmacologie)</term><term>Alanine (analogues et dérivés)</term><term>Alanine (pharmacologie)</term><term>Animaux</term><term>Antiviraux (pharmacologie)</term><term>Charge virale</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie)</term><term>Infections à coronavirus ()</term><term>Infections à coronavirus (traitement médicamenteux)</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Pandémies</term><term>Pneumopathie virale</term><term>Poumon (anatomopathologie)</term><term>Poumon (virologie)</term><term>Prophylaxie après exposition</term><term>Réplication virale ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Adenosine Monophosphate</term><term>Alanine</term><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>AMP</term><term>Alanine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>AMP</term><term>Alanine</term><term>Antiviraux</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Coronavirus Infections</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Betacoronavirus</term><term>Disease Models, Animal</term><term>Macaca mulatta</term><term>Male</term><term>Pandemics</term><term>Pneumonia, Viral</term><term>Post-Exposure Prophylaxis</term><term>Viral Load</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Charge virale</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Infections à coronavirus</term><term>Macaca mulatta</term><term>Modèles animaux de maladie humaine</term><term>Mâle</term><term>Pandémies</term><term>Pneumopathie virale</term><term>Prophylaxie après exposition</term><term>Réplication virale</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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