tetano
Editor, Senior Moderator
Antimicrob Agents Chemother
. 2022 Jun 16;e0019822.
doi: 10.1128/aac.00198-22. Online ahead of print.
In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
Liva Checkmahomed[SUP] 1 [/SUP], Julie Carbonneau[SUP] 1 [/SUP], Venice Du Pont[SUP] 2 [/SUP], Nicholas C Riola[SUP] 2 [/SUP], Jason K Perry[SUP] 2 [/SUP], Jiani Li[SUP] 2 [/SUP], Bastien Paré[SUP] 3 [/SUP], Shawn M Simpson[SUP] 3 [/SUP], Martin A Smith[SUP] 3 [/SUP], Danielle P Porter[SUP] 2 [/SUP], Guy Boivin[SUP] 1 [/SUP]
Affiliations
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[SUB]50[/SUB]). When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold increase in EC[SUB]50[/SUB] was observed, indicating a high in vitro barrier to remdesivir resistance.
Keywords: Nsp12 polymerase; SARS-CoV-2; remdesivir; resistance.
. 2022 Jun 16;e0019822.
doi: 10.1128/aac.00198-22. Online ahead of print.
In Vitro Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
Liva Checkmahomed[SUP] 1 [/SUP], Julie Carbonneau[SUP] 1 [/SUP], Venice Du Pont[SUP] 2 [/SUP], Nicholas C Riola[SUP] 2 [/SUP], Jason K Perry[SUP] 2 [/SUP], Jiani Li[SUP] 2 [/SUP], Bastien Paré[SUP] 3 [/SUP], Shawn M Simpson[SUP] 3 [/SUP], Martin A Smith[SUP] 3 [/SUP], Danielle P Porter[SUP] 2 [/SUP], Guy Boivin[SUP] 1 [/SUP]
Affiliations
- PMID: 35708323
- DOI: 10.1128/aac.00198-22
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[SUB]50[/SUB]). When V166L was introduced into a recombinant SARS-CoV-2 virus, a 1.5-fold increase in EC[SUB]50[/SUB] was observed, indicating a high in vitro barrier to remdesivir resistance.
Keywords: Nsp12 polymerase; SARS-CoV-2; remdesivir; resistance.