February 8, 2021

Genetic Conservation of SARS-CoV-2 RNA Replication Complex in Globally Circulating Isolates and Recently Emerged Variants from Humans and Minks Suggests Minimal Pre-Existing Resistance to Remdesivir

Category: Article Summary

Topic: Testing and Treatment

Keywords (Tags): treatment, variants

A study analyzing the genetic diversity of the RNA replication complex that is targeted by the antiviral drug remdesivir in a large set of human SARS-CoV-2 isolates (n > 90,000), including the B.1.1.7 and 501.V2 variants and mink isolate (n>300) sequences, found that previously-identified amino acid substitutions that caused reduced susceptibility to remdesivir in-vitro were observed at very low frequencies (0.002%). There was low genetic variation in the complex in both humans and mink isolates. Furthermore, among the sequence variants observed in ≥0.5% clinical isolates, none were located near the established polymerase active site or sites critical for remdesivir activity, suggesting low risk of pre-existing SARS-CoV-2 remdesivir resistance.

Martin et al. (Feb 2021). Genetic Conservation of SARS-CoV-2 RNA Replication Complex in Globally Circulating Isolates and Recently Emerged Variants from Humans and Minks Suggests Minimal Pre-Existing Resistance to Remdesivir. Antiviral Research. https://doi.org/10.1016/j.antiviral.2021.105033