Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice
Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice
SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM). Weaker activity was observed in Vero E6 cells (EC50 = 1.65 μM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.
Leist Sarah R.、Sch?fer Alexandra、Dinnon Kenneth H. III、Pruijssers Andrea J.、Porter Danielle P.、Pitts Jared、Cihlar Tomas、Murakami Eisuke、Feng Joy Y.、Bilello John P.、Gralinksi Lisa E.、Agostini Maria L.、Chappell James D.、Gully Kendra、Martinez David R.、Brown Ariane J.、Graham Rachel L.、Du Pont Venice、Babusis Darius、Ma Bin、Denison Mark R.、Baric Ralph S.、Lu Xiaotao、Hughes Tia M.、George Amelia S.、Sheahan Timothy P.、Yount Boyd L.、Stevens Laura J.、Perry Jason K.
Department of Epidemiology, University of North Carolina at Chapel HillDepartment of Epidemiology, University of North Carolina at Chapel HillDepartment of Epidemiology, University of North Carolina at Chapel Hill||Department of Microbiology and Immunology, University of North Carolina at Chapel HillDepartment of Pediatrics, Vanderbilt University Medical Center||Vanderbilt Institute for Infection, Immunology, and InflammationGilead Sciences, IncGilead Sciences, IncGilead Sciences, IncGilead Sciences, IncGilead Sciences, IncGilead Sciences, IncDepartment of Epidemiology, University of North Carolina at Chapel HillDepartment of Pediatrics, Vanderbilt University Medical Center||Vanderbilt Institute for Infection, Immunology, and InflammationDepartment of Pediatrics, Vanderbilt University Medical Center||Vanderbilt Institute for Infection, Immunology, and InflammationDepartment of Epidemiology, University of North Carolina at Chapel HillDepartment of Epidemiology, University of North Carolina at Chapel HillDepartment of Epidemiology, University of North Carolina at Chapel HillDepartment of Epidemiology, University of North Carolina at Chapel HillGilead Sciences, IncGilead Sciences, IncGilead Sciences, IncDepartment of Pediatrics, Vanderbilt University Medical Center||Vanderbilt Institute for Infection, Immunology, and Inflammation||Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical CenterDepartment of Epidemiology, University of North Carolina at Chapel Hill||Department of Microbiology and Immunology, University of North Carolina at Chapel HillDepartment of Pediatrics, Vanderbilt University Medical Center||Vanderbilt Institute for Infection, Immunology, and InflammationDepartment of Pediatrics, Vanderbilt University Medical Center||Vanderbilt Institute for Infection, Immunology, and InflammationDepartment of Pediatrics, Vanderbilt University Medical Center||Vanderbilt Institute for Infection, Immunology, and InflammationDepartment of Epidemiology, University of North Carolina at Chapel HillDepartment of Epidemiology, University of North Carolina at Chapel HillDepartment of Pediatrics, Vanderbilt University Medical Center||Vanderbilt Institute for Infection, Immunology, and InflammationGilead Sciences, Inc
医药卫生理论医学研究方法药学
COVID-19SARS-CoV-2coronavirusantiviralsremdesivirRdRpRNA-dependent RNA polymerasetherapeuticmouse
Leist Sarah R.,Sch?fer Alexandra,Dinnon Kenneth H. III,Pruijssers Andrea J.,Porter Danielle P.,Pitts Jared,Cihlar Tomas,Murakami Eisuke,Feng Joy Y.,Bilello John P.,Gralinksi Lisa E.,Agostini Maria L.,Chappell James D.,Gully Kendra,Martinez David R.,Brown Ariane J.,Graham Rachel L.,Du Pont Venice,Babusis Darius,Ma Bin,Denison Mark R.,Baric Ralph S.,Lu Xiaotao,Hughes Tia M.,George Amelia S.,Sheahan Timothy P.,Yount Boyd L.,Stevens Laura J.,Perry Jason K..Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2020.04.27.064279.点此复制
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