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Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants.
Pitts, Jared; Li, Jiani; Perry, Jason K; Du Pont, Venice; Riola, Nicholas; Rodriguez, Lauren; Lu, Xianghan; Kurhade, Chaitanya; Xie, Xuping; Camus, Gregory; Manhas, Savrina; Martin, Ross; Shi, Pei-Yong; Cihlar, Tomas; Porter, Danielle P; Mo, Hongmei; Maiorova, Evguenia; Bilello, John P.
  • Pitts J; Gilead Sciences, Inc., Foster City, California, USA.
  • Li J; Gilead Sciences, Inc., Foster City, California, USA.
  • Perry JK; Gilead Sciences, Inc., Foster City, California, USA.
  • Du Pont V; Gilead Sciences, Inc., Foster City, California, USA.
  • Riola N; Gilead Sciences, Inc., Foster City, California, USA.
  • Rodriguez L; Gilead Sciences, Inc., Foster City, California, USA.
  • Lu X; Gilead Sciences, Inc., Foster City, California, USA.
  • Kurhade C; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Xie X; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Camus G; Gilead Sciences, Inc., Foster City, California, USA.
  • Manhas S; Gilead Sciences, Inc., Foster City, California, USA.
  • Martin R; Gilead Sciences, Inc., Foster City, California, USA.
  • Shi PY; Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Cihlar T; Gilead Sciences, Inc., Foster City, California, USA.
  • Porter DP; Gilead Sciences, Inc., Foster City, California, USA.
  • Mo H; Gilead Sciences, Inc., Foster City, California, USA.
  • Maiorova E; Gilead Sciences, Inc., Foster City, California, USA.
  • Bilello JP; Gilead Sciences, Inc., Foster City, California, USA.
Antimicrob Agents Chemother ; 66(6): e0022222, 2022 06 21.
Article in English | MEDLINE | ID: covidwho-1832332
ABSTRACT
Genetic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence and rapid spread of multiple variants throughout the pandemic, of which Omicron is currently the predominant variant circulating worldwide. SARS-CoV-2 variants of concern/variants of interest (VOC/VOI) have evidence of increased viral transmission, disease severity, or decreased effectiveness of vaccines and neutralizing antibodies. Remdesivir (RDV [VEKLURY]) is a nucleoside analog prodrug and the first FDA-approved antiviral treatment of COVID-19. Here, we present a comprehensive antiviral activity assessment of RDV and its parent nucleoside, GS-441524, against 10 current and former SARS-CoV-2 VOC/VOI clinical isolates by nucleoprotein enzyme-linked immunosorbent assay (ELISA) and plaque reduction assay. Delta and Omicron variants remained susceptible to RDV and GS-441524, with 50% effective concentration (EC50) values 0.30- to 0.62-fold of those observed against the ancestral WA1 isolate. All other tested variants exhibited EC50 values ranging from 0.13- to 2.3-fold of the observed EC50 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Antimicrob Agents Chemother Year: 2022 Document Type: Article Affiliation country: Aac.00222-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Antimicrob Agents Chemother Year: 2022 Document Type: Article Affiliation country: Aac.00222-22