<i>In Vitro</i> Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance-Reference-Cited by-同舟云学术

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

Published:2022-07-19 Issue:7 Volume:66 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Checkmahomed Liva¹,Carbonneau Julie¹,Du Pont Venice²,Riola Nicholas C.²,Perry Jason K.²,Li Jiani²,Paré Bastien³,Simpson Shawn M.³,Smith Martin A.³,Porter Danielle P.²,Boivin Guy¹^ORCID

Affiliation:

1. CHU de Quebec Hospital and Laval University, Quebec City, Quebec, Canada

2. Gilead Sciences, Foster City, California, USA

3. Ste-Justine Hospital and University of Montréal, Montréal, Quebec, Canada

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 (EC 50 ).

Funder

Canadian Institute of Health Research

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/aac.00198-22

Reference17 articles.

1. Remdesivir for the Treatment of Covid-19 — Final Report

2. Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit

3. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease