Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants
Jared Pitts, Jiani Li, Jason K. Perry, Venice Du Pont, Nicholas C. Riola, Lauren Rodriguez, Xianghan Lu, Chaitanya Kurhade, Xuping Xie, Grégory Camus, Savrina Manhas, Ross Martin, Pei‐Yong Shi, Tomáš Cihlář, Danielle Porter, Hongmei Mo, Evguenia Maiorova, John P. Bilello
Abstract
values against WA1. Analysis of nearly 6 million publicly available variant isolate sequences confirmed that Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, is highly conserved across variants, with only 2 prevalent changes (P323L and G671S). Using recombinant viruses, both RDV and GS-441524 retained potency against all viruses containing frequent variant substitutions or their combination. Taken together, these results highlight the conserved nature of SARS-CoV-2 Nsp12 and provide evidence of sustained SARS-CoV-2 antiviral activity of RDV and GS-441524 across the tested variants. The observed pan-variant activity of RDV supports its continued use for the treatment of COVID-19 regardless of the SARS-CoV-2 variant.