ArticlePLoS pathogens2021
In vitro selection of Remdesivir resistance suggests evolutionary predictability of SARS-CoV-2.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed.
- Virologic insights from the phase 3 REDPINE trial: remdesivir in renally impaired and immunocompromised patients with COVID-19.Antimicrobial agents and chemotherapy · 2026Trial
- SARS-CoV-2 resistance analyses from the Phase 3 PINETREE study of remdesivir treatment in nonhospitalized participants.Antimicrobial agents and chemotherapy · 2025Trial
- No Remdesivir Resistance Observed in the Phase 3 Severe and Moderate COVID-19 SIMPLE Trials.Viruses · 2024Trial
- Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1).The Journal of infectious diseases · 2023Trial
- Article
- Cross-resistance patterns in SARS-CoV-2 against 3CL protease inhibitors.Nature communications · 2026Article
- Biochanin A Exerts Broad-Spectrum Antiviral Activity Against Coronaviruses via Activating the AMPK/Nrf2/GSH Pathway.Microorganisms · 2026Article
- Antivirals Targeting Coronavirus RNA-Dependent RNA Polymerase and Main Protease: From Mechanisms of Action to Outcomes in COVID-19 Clinical Trials.Microbial biotechnology · 2026Review
- Ordinary differential equation models of SARS-CoV-2 replication dynamics and antiviral drug efficacies.Npj viruses · 2026Review
- Stalling the Enemy: Targeting Nsp13 for Next-Generation SARS-CoV-2 Antivirals.International journal of molecular sciences · 2026Article
- Role of remdesivir for the treatment of COVID-19 in patients with hematologic malignancy-A narrative review and expert opinion.European journal of clinical investigation · 2025Review
- Review
- SARS-CoV-2 Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug Resistance.Viruses · 2025Article
- Mycophenolic acid treatment drives the emergence of novel SARS-CoV-2 variants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Host-Virus Interface in Persistent SARS-CoV-2 Infections: Viral Characteristic Evolution and Gene Expression Profiling Analysis.International journal of molecular sciences · 2025Article
- Evolution of Antiviral Drug Resistance in SARS-CoV-2.Viruses · 2025Review
- The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in severe models of COVID-19.Microbiology spectrum · 2025Article
- EfficientAntimicrobial agents and chemotherapy · 2025Article
- SARS-CoV-2 drug resistance and therapeutic approaches.Heliyon · 2025Review
- The impact of remdesivir on SARS-CoV-2 evolution in vivo.JCI insight · 2025Article
51 more citing papers are in PubMed but not listed here.
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20 authors.
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Abstract
Remdesivir (RDV), a broadly acting nucleoside analogue, is the only FDA approved small molecule antiviral for the treatment of COVID-19 patients. To date, there are no reports identifying SARS-CoV-2 RDV resistance in patients, animal models or in vitro. Here, we selected drug-resistant viral populations by serially passaging SARS-CoV-2 in vitro in the presence of RDV. Using high throughput sequencing, we identified a single mutation in RNA-dependent RNA polymerase (NSP12) at a residue conserved among all coronaviruses in two independently evolved populations displaying decreased RDV sensitivity. Introduction of the NSP12 E802D mutation into our SARS-CoV-2 reverse genetics backbone confirmed its role in decreasing RDV sensitivity in vitro. Substitution of E802 did not affect viral replication or activity of an alternate nucleoside analogue (EIDD2801) but did affect virus fitness in a competition assay. Analysis of the globally circulating SARS-CoV-2 variants (>800,000 sequences) showed no evidence of widespread transmission of RDV-resistant mutants. Surprisingly, we observed an excess of substitutions in spike at corresponding sites identified in the emerging SARS-CoV-2 variants of concern (i.e., H69, E484, N501, H655) indicating that they can arise in vitro in the absence of immune selection. The identification and characterisation of a drug resistant signature within the SARS-CoV-2 genome has implications for clinical management and virus surveillance.
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