Multiple variations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had emerged and spread rapidly across the pandemic, with Omicron being the most prevalent version now circulating worldwide. Remdesivir (RDV [VEKLURY]) was a nucleoside analog prodrug and the first antiviral medication for COVID-19 to be licensed by the FDA. Researchers used a nucleoprotein enzyme-linked immunosorbent test (ELISA) and plaque reduction assay to investigate the antiviral efficacy of RDV and its parent nucleoside, GS-441524, against ten current and past SARS-CoV-2 VOC/VOI clinical isolates. RDV and GS-441524 remained vulnerable to Delta and Omicron variations, with 50% effective concentration (EC50) values 0.30 to 0.62-fold higher than the original WA1 isolate. The EC50 values for all other variants examined ranged from 0.13 to 2.3 times those obtained against WA1. Nsp12, the RNA-dependent RNA polymerase (RdRp) target of RDV and GS-441524, was substantially conserved across variants, according to an analysis of almost 6 million publically available variant isolate sequences (P323L and G671S). Both RDV and GS-441524 retained efficacy against all viruses featuring frequent variant substitutions or combinations when tested with recombinant viruses. The outcomes illustrated the conserved nature of SARS-CoV-2 Nsp12 and showed that RDV and GS-441524 had consistent antiviral action against SARS-CoV-2 across all variants examined. RDV’s pan-variant activity suggested that it should be used for COVID-19 treatment independently of the SARS-CoV-2 variant.
Source:journals.asm.org/doi/10.1128/aac.00222-22
