ArticleNature communications2021
Mechanism of SARS-CoV-2 polymerase stalling by remdesivir.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 350 papers, 1 of them a synthesis that pooled it.
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Who cites it
350 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials.The Lancet. Respiratory medicine · 2023Pooled it
- No Remdesivir Resistance Observed in the Phase 3 Severe and Moderate COVID-19 SIMPLE Trials.Viruses · 2024Trial
- Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial.Nature communications · 2022Trial
- Recent advances in functional studies of coronavirus NSP13 helicase and challenges in inhibitor development.Virulence · 2026Review
- An efficient and versatile reverse genetics system for bovine coronavirus facilitates antiviral evaluation.Veterinary research · 2026Article
- Molecular Insights into High-Pathogenicity RNA Viruses.Viruses · 2026Review
- Coronavirus NSP14 drives internal m7G modification to rewire host splicing and promote viral replication.Nucleic acids research · 2026Article
- Substrate and target selectivity of 4'-fluoroadenosine against viral and host polymerases.The Journal of biological chemistry · 2026Article
- Host-directed antiviral strategy targeting prohibitins: Mel56 suppresses influenza A virus and severe acute respiratory syndrome coronavirus 2 via modulation of antioxidant pathways and mitochondrial function.Microbiology spectrum · 2026Article
- Article
- Copy-back RNA synthesis by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.Science advances · 2026Article
- RNA with Azvudine Incorporated One Nucleotide Upstream of 3'-End Resists Cleavage by SARS-CoV-2 Proofreading Exonuclease.Research square · 2026Article
- RNA virus polymerase-helicase coupling enables rapid elongation through duplex RNA.Cell reports · 2026Article
- Preferential remdesivir triphosphate incorporation by SARS-CoV-2 polymerase is altered to ATP by the S759A mutation.Communications biology · 2026Article
- SAMHD1 depletion restricts SARS-CoV-2 infection by suppressing HNF1-dependent ACE2 expression in lung epithelial cells.PLoS pathogens · 2026Article
- Pyrogallol B-ring enhances catechin binding to the SARS-CoV-2 spike receptor-binding domain to inhibit interaction with ACE2.Scientific reports · 2026Article
- SARS-CoV-2 Error Catastrophe Under Molnupiravir: Mutagenic Enhancement Enables Viral Persistence with Impaired Fitness.Viruses · 2026Article
- 1'- and 4'-Cyano Modified Adenosine Analogs Against Prototypic Flavivirus RNA-Dependent RNA Polymerases.Viruses · 2026Article
- NS5-targeting nucleoside analogs inhibit dengue virus and other flaviviruses.PLoS pathogens · 2026Article
- Remdesivir in COVID-19: pros and cons.Frontiers in pharmacology · 2026Review
290 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls. Here we use synthetic RNA chemistry, biochemistry and cryo-electron microscopy to establish the molecular mechanism of remdesivir-induced RdRp stalling. We show that addition of the fourth nucleotide following remdesivir incorporation into the RNA product is impaired by a barrier to further RNA translocation. This translocation barrier causes retention of the RNA 3'-nucleotide in the substrate-binding site of the RdRp and interferes with entry of the next nucleoside triphosphate, thereby stalling RdRp. In the structure of the remdesivir-stalled state, the 3'-nucleotide of the RNA product is matched and located with the template base in the active center, and this may impair proofreading by the viral 3'-exonuclease. These mechanistic insights should facilitate the quest for improved antivirals that target coronavirus replication.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.