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In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance.
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.
  • Checkmahomed L; CHU de Quebec Hospital and Laval University, Quebec City, Quebec, Canada.
  • Carbonneau J; CHU de Quebec Hospital and Laval University, Quebec City, Quebec, Canada.
  • Du Pont V; Gilead Sciences, Foster City, California, USA.
  • Riola NC; Gilead Sciences, Foster City, California, USA.
  • Perry JK; Gilead Sciences, Foster City, California, USA.
  • Li J; Gilead Sciences, Foster City, California, USA.
  • Paré B; Ste-Justine Hospital and University of Montréal, Montréal, Quebec, Canada.
  • Simpson SM; Ste-Justine Hospital and University of Montréal, Montréal, Quebec, Canada.
  • Smith MA; Ste-Justine Hospital and University of Montréal, Montréal, Quebec, Canada.
  • Porter DP; Gilead Sciences, Foster City, California, USA.
  • Boivin G; CHU de Quebec Hospital and Laval University, Quebec City, Quebec, Canada.
Antimicrob Agents Chemother ; 66(7): e0019822, 2022 07 19.
Article in English | MEDLINE | ID: covidwho-1901915
ABSTRACT
In vitro 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 (EC50). When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold increase in EC50 was observed, indicating a high in vitro barrier to remdesivir resistance.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Limits: Humans Language: English Journal: Antimicrob Agents Chemother Year: 2022 Document Type: Article Affiliation country: Aac.00198-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Limits: Humans Language: English Journal: Antimicrob Agents Chemother Year: 2022 Document Type: Article Affiliation country: Aac.00198-22