Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice.
Andrea J. Pruijssers,
Amelia S George,
Sarah R. Leist,
Lisa E. Gralinksi,
Kenneth H. Dinnon,
Boyd L. Yount,
Maria L Agostini,
Laura J Stevens,
James D. Chappell,
Tia M Hughes,
David R. Martinez,
Ariane J Brown,
Rachel L. Graham,
Jason K Perry,
Venice Du Pont,
Joy Y Feng,
John P Bilello,
Danielle P Porter,
Ralph S. Baric,
Mark R. Denison,
Timothy P. Sheahan
Posted 27 Apr 2020
bioRxiv DOI: 10.1101/2020.04.27.064279 (published DOI: 10.1016/j.celrep.2020.107940)
Posted 27 Apr 2020
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 substantial 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. ### Competing Interest Statement The authors affiliated with Gilead Sciences, Inc. are employees of the company and own company stock. The other authors have no conflict of interest to report.
- Downloaded 4,321 times
- Download rankings, all-time:
- Site-wide: 1,193 out of 103,764
- In microbiology: 148 out of 9,238
- Year to date:
- Site-wide: 356 out of 103,764
- Since beginning of last month:
- Site-wide: 1,657 out of 103,764
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!