ArticleeLife2021
Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 77 citations in OpenAlex.
- Distinct modes of RNA degradation by the structurally related coronavirus and arenavirus exoribonucleases.Journal of virology · 2026Article
- The nucleoside analog CMX521 inhibits coronavirus RNA-dependent RNA polymerase via a two-pronged mechanism.bioRxiv : the preprint server for biology · 2026Article
- 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
- Article
- Preferential remdesivir triphosphate incorporation by SARS-CoV-2 polymerase is altered to ATP by the S759A mutation.Communications biology · 2026Article
- Omega Nucleic Acids (ΩNA), Ultimate Nucleic Acids for Future Technology.Molecules (Basel, Switzerland) · 2026Review
- Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals.Nature communications · 2026Article
- Structural basis for selective remdesivir incorporation by SARS-CoV-2 polymerase, and S759A resistance.Research square · 2025Article
- Template switching by coronavirus polymerase requires helicase activity and is stimulated by remdesivir and molnupiravir.bioRxiv : the preprint server for biology · 2025Article
- Article
- A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.Nucleic acids research · 2025Article
- Mechanistic insights into the activity of SARS-CoV-2 RNA polymerase inhibitors using single-molecule FRET.Nucleic acids research · 2025Article
- SARS-CoV-2: The Interplay Between Evolution and Host Immunity.Annual review of immunology · 2025Review
- Development of 3'-Deoxy-3',4'-didehydro-nucleoside Prodrug Inhibitors of West Nile and Zika Viruses.ACS medicinal chemistry letters · 2024Article
- An alphacoronavirus polymerase structure reveals conserved replication factor functions.Nucleic acids research · 2024Article
- The oral nucleoside prodrug GS-5245 is efficacious against SARS-CoV-2 and other endemic, epidemic, and enzootic coronaviruses.Science translational medicine · 2024Article
- Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.Science advances · 2024Article
- ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover.Nature communications · 2024Article
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 5 countries.
Funding
Abstract
The absence of 'shovel-ready' anti-coronavirus drugs during vaccine development has exceedingly worsened the SARS-CoV-2 pandemic. Furthermore, new vaccine-resistant variants and coronavirus outbreaks may occur in the near future, and we must be ready to face this possibility. However, efficient antiviral drugs are still lacking to this day, due to our poor understanding of the mode of incorporation and mechanism of action of nucleotides analogs that target the coronavirus polymerase to impair its essential activity. Here, we characterize the impact of remdesivir (RDV, the only FDA-approved anti-coronavirus drug) and other nucleotide analogs (NAs) on RNA synthesis by the coronavirus polymerase using a high-throughput, single-molecule, magnetic-tweezers platform. We reveal that the location of the modification in the ribose or in the base dictates the catalytic pathway(s) used for its incorporation. We show that RDV incorporation does not terminate viral RNA synthesis, but leads the polymerase into backtrack as far as 30 nt, which may appear as termination in traditional ensemble assays. SARS-CoV-2 is able to evade the endogenously synthesized product of the viperin antiviral protein, ddhCTP, though the polymerase incorporates this NA well. This experimental paradigm is essential to the discovery and development of therapeutics targeting viral polymerases.
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Registered trials
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.