SARS-CoV-2 diversification after antiviral administration revealed strong selection for the nonsynonymous G671S mutation in nsp12, according to a single-center, retrospective cohort study published in JCI Insight.
The impact of remdesivir on viral evolution in vivo had remained unclear before Ted Ling-Hu and colleagues assessed SARS-CoV-2 diversity over time. Researchers performed whole-genome sequencing on 98 paired specimens collected from 49 hospitalized patients both before and after they received remdesivir. Genetic divergence between paired specimens showed no significant difference compared with a control group of patients who did not receive the antiviral drug.
When investigators focused on minority variants, however, several positions showed preferential diversification following treatment. Most notably, remdesivir administration resulted in strong selection for the G671S mutation in nsp12, which researchers associated with enhanced viral fitness. Investigators also found this same mutation enriched in a second cohort of 143 inpatients whose specimens were collected after receiving remdesivir.
Only one other mutation previously implicated in drug resistance, nsp12:V792I, was preferentially selected for after remdesivir administration. These findings suggest that SARS-CoV-2 variants with enhanced replicative fitness may be selected for in the presence of antiviral therapy as an indirect means to overcome selective pressure.
- Viral genome sequencing of 98 paired specimens showed that standard genetic divergence did not significantly increase after remdesivir treatment.
- Targeted analysis revealed that minority viral variants, specifically the nsp12 G671S mutation, experienced strong selection pressure during therapy.
- The identified G671S and V792I mutations indicate that variants with enhanced replicative fitness may emerge in patients receiving antiviral therapy.
| Cohort Group | Patient Sample Size (N) | Key Mutations Identified |
|---|---|---|
| Primary Paired Cohort | 49 patients (98 specimens) | nsp12:G671S, nsp12:V792I |
| Secondary Validation Cohort | 143 inpatients | Enriched nsp12:G671S |
- Ling-Hu, T., et al. The impact of remdesivir on SARS-CoV-2 evolution in vivo. JCI Insight.
