tetano
Editor, Senior Moderator
Cell Rep
. 2020 Jul 7;107940.
doi: 10.1016/j.celrep.2020.107940. Online ahead of print.
Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice
Andrea J Pruijssers[SUP] 1 [/SUP], Amelia S George[SUP] 2 [/SUP], Alexandra Sch?fer[SUP] 3 [/SUP], Sarah R Leist[SUP] 3 [/SUP], Lisa E Gralinksi[SUP] 3 [/SUP], Kenneth H Dinnon 3rd[SUP] 4 [/SUP], Boyd L Yount[SUP] 3 [/SUP], Maria L Agostini[SUP] 2 [/SUP], Laura J Stevens[SUP] 2 [/SUP], James D Chappell[SUP] 2 [/SUP], Xiaotao Lu[SUP] 2 [/SUP], Tia M Hughes[SUP] 2 [/SUP], Kendra Gully[SUP] 3 [/SUP], David R Martinez[SUP] 3 [/SUP], Ariane J Brown[SUP] 3 [/SUP], Rachel L Graham[SUP] 3 [/SUP], Jason K Perry[SUP] 5 [/SUP], Venice Du Pont[SUP] 5 [/SUP], Jared Pitts[SUP] 5 [/SUP], Bin Ma[SUP] 5 [/SUP], Darius Babusis[SUP] 5 [/SUP], Eisuke Murakami[SUP] 5 [/SUP], Joy Y Feng[SUP] 5 [/SUP], John P Bilello[SUP] 5 [/SUP], Danielle P Porter[SUP] 5 [/SUP], Tomas Cihlar[SUP] 5 [/SUP], Ralph S Baric[SUP] 4 [/SUP], Mark R Denison[SUP] 6 [/SUP], Timothy P Sheahan[SUP] 7 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC[SUB]50[/SUB] = 0.01 μM). Weaker activity is observed in Vero E6 cells (EC[SUB]50[/SUB] = 1.65 μM) because of 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 the chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared with vehicle-treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.
Keywords: COVID-19; GS-441524; RNA-dependent RNA polymerase; RdRp; SARS-CoV-2; antiviral; coronavirus; mouse; remdesivir; therapeutic.
. 2020 Jul 7;107940.
doi: 10.1016/j.celrep.2020.107940. Online ahead of print.
Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice
Andrea J Pruijssers[SUP] 1 [/SUP], Amelia S George[SUP] 2 [/SUP], Alexandra Sch?fer[SUP] 3 [/SUP], Sarah R Leist[SUP] 3 [/SUP], Lisa E Gralinksi[SUP] 3 [/SUP], Kenneth H Dinnon 3rd[SUP] 4 [/SUP], Boyd L Yount[SUP] 3 [/SUP], Maria L Agostini[SUP] 2 [/SUP], Laura J Stevens[SUP] 2 [/SUP], James D Chappell[SUP] 2 [/SUP], Xiaotao Lu[SUP] 2 [/SUP], Tia M Hughes[SUP] 2 [/SUP], Kendra Gully[SUP] 3 [/SUP], David R Martinez[SUP] 3 [/SUP], Ariane J Brown[SUP] 3 [/SUP], Rachel L Graham[SUP] 3 [/SUP], Jason K Perry[SUP] 5 [/SUP], Venice Du Pont[SUP] 5 [/SUP], Jared Pitts[SUP] 5 [/SUP], Bin Ma[SUP] 5 [/SUP], Darius Babusis[SUP] 5 [/SUP], Eisuke Murakami[SUP] 5 [/SUP], Joy Y Feng[SUP] 5 [/SUP], John P Bilello[SUP] 5 [/SUP], Danielle P Porter[SUP] 5 [/SUP], Tomas Cihlar[SUP] 5 [/SUP], Ralph S Baric[SUP] 4 [/SUP], Mark R Denison[SUP] 6 [/SUP], Timothy P Sheahan[SUP] 7 [/SUP]
Affiliations
- PMID: 32668216
- DOI: 10.1016/j.celrep.2020.107940
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC[SUB]50[/SUB] = 0.01 μM). Weaker activity is observed in Vero E6 cells (EC[SUB]50[/SUB] = 1.65 μM) because of 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 the chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared with vehicle-treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.
Keywords: COVID-19; GS-441524; RNA-dependent RNA polymerase; RdRp; SARS-CoV-2; antiviral; coronavirus; mouse; remdesivir; therapeutic.