An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice
Timothy P. Sheahan, Amy Sims, Shuntai Zhou, Rachel L. Graham, Andrea J. Pruijssers, Maria L. Agostini, Sarah R. Leist, Alexandra Schäfer, Kenneth H. Dinnon, Laura J. Stevens, James D. Chappell, Xiaotao Lu, Tia M. Hughes, Amelia S. George, Collin S Hill, Stephanie A. Montgomery, Ariane J. Brown, Gregory R. Bluemling, Michael G. Natchus, Manohar Saindane, Alexander A. Kolykhalov, George R. Painter, Jennifer L. Harcourt, Azaibi Tamin, Natalie J. Thornburg, Ronald Swanstrom, Mark R. Denison, Ralph S. Baric
Abstract
-hydroxycytidine-5'-isopropyl ester), improved pulmonary function and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral, but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple CoVs and oral bioavailability highlights its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic CoVs.