In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance

selection of remdesivir-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the emergence of a V166L substitution, located outside of the polymerase active site of the Nsp12 protein, after 9 passages of a single lineage. V166L remained the only Nsp12 substitution after 17...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2022-07, Vol.66 (7), p.e0019822-e0019822
Main Authors: Checkmahomed, Liva, Carbonneau, Julie, Du Pont, Venice, Riola, Nicholas C, Perry, Jason K, Li, Jiani, Paré, Bastien, Simpson, Shawn M, Smith, Martin A, Porter, Danielle P, Boivin, Guy
Format: Article
Language:English
Subjects:
Antiviral Agents
Virology
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Summary:selection of remdesivir-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the emergence of a V166L substitution, located outside of the polymerase active site of the Nsp12 protein, after 9 passages of a single lineage. V166L remained the only Nsp12 substitution after 17 passages (10 μM remdesivir), conferring a 2.3-fold increase in 50% effective concentration (EC ). When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold increase in EC was observed, indicating a high barrier to remdesivir resistance.
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.00198-22