Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice

Authors: 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 L. 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 Porter, Tomáš Cihlář, Ralph S. Baric, Mark R. Denison, Timothy P. Sheahan - Cell Reports 2020 cited by 540

= 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.