Authors: Laura J. Stevens, Andrea J. Pruijssers, Hery W. Lee, Calvin J. Gordon, Egor P. Tchesnokov, Jennifer Gribble, Amelia S. George, Tia M. Hughes, Xiaotao Lu, Jiani Li, Jason K. Perry, Danielle P. Porter, Tomas Cihlar, Timothy P. Sheahan, Ralph S. Baric, Matthias Götte, Mark R. Denison
Published: 2022-04-28
DOI: 10.1126/scitranslmed.abo0718
Source: Full article
The nucleoside analog remdesivir (RDV) is a Food and Drug Administration–approved antiviral for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, it is critical to understand factors that promote or prevent RDV resistance. We passaged SARS-CoV-2 in the presence of increasing concentrations of GS-441524, the parent nucleoside of RDV. After 13 passages, we isolated three viral lineages with phenotypic resistance as defined by increases in half-maximal effective concentration from 2.7- to 10.4-fold. Sequence analysis identified nonsynonymous mutations in nonstructural protein 12 RNA-dependent RNA polymerase (