• Andrea J Pruijssers, Amelia S George, Alexandra Schäfer, Sarah R Leist, Lisa E Gralinksi, Kenneth H Dinnon, Boyd L Yount, Maria L Agostini, Laura J Stevens, James D Chappell, Xiaotao Lu, Tia M Hughes, Kendra Gully, David R Martinez, Ariane J Brown, Rachel L Graham, Jason K Perry, Venice Du Pont, Jared Pitts, Bin Ma, Darius Babusis, Eisuke Murakami, Joy Y Feng, John P Bilello, Danielle P Porter, Tomas Cihlar, Ralph S Baric, Mark R Denison, and Timothy P Sheahan.
• Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, TN 37232, USA. Electronic address: ardina.pruijssers@vumc.org.
• Cell Rep. 2020 Jul 21; 32 (3): 107940.

AbstractSevere 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.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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