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

Antimicrob Agents Chemother. 2022 Jul 19;66(7):e0019822. doi: 10.1128/aac.00198-22. Epub 2022 Jun 16.

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.

Keywords: Nsp12 polymerase; SARS-CoV-2; remdesivir; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / chemistry
  • Alanine / analogs & derivatives
  • Alanine / metabolism
  • Antiviral Agents / chemistry
  • COVID-19 Drug Treatment*
  • Humans
  • SARS-CoV-2*

Substances

  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Alanine

Grants and funding