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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 1 , Amelia S George 2 , Alexandra Sch?fer 3 , Sarah R Leist 3 , Lisa E Gralinksi 3 , Kenneth H Dinnon 3rd 4 , Boyd L Yount 3 , Maria L Agostini 2 , Laura J Stevens 2 , James D Chappell 2 , Xiaotao Lu 2 , Tia M Hughes 2 , Kendra Gully 3 , David R Martinez 3 , Ariane J Brown 3 , Rachel L Graham 3 , Jason K Perry 5 , Venice Du Pont 5 , Jared Pitts 5 , Bin Ma 5 , Darius Babusis 5 , Eisuke Murakami 5 , Joy Y Feng 5 , John P Bilello 5 , Danielle P Porter 5 , Tomas Cihlar 5 , Ralph S Baric 4 , Mark R Denison 6 , Timothy P Sheahan 7
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 (EC50 = 0.01 μM). Weaker activity is observed in Vero E6 cells (EC50 = 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.