ArticleProceedings of the National Academy of Sciences of the United States of America2022
Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
108 citing papers in PubMed, 186 citations in OpenAlex.
- Characterization of Treatment Resistance and Viral Kinetics in the Setting of Single-Active Versus Dual-Active Monoclonal Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2.The Journal of infectious diseases · 2024Trial
- Distinct modes of RNA degradation by the structurally related coronavirus and arenavirus exoribonucleases.Journal of virology · 2026Article
- Structural and Mechanistic Perspectives on SARS-CoV-2 Nonstructural Protein 14-Mediated Cap Formation and Drug Discovery.Microorganisms · 2026Review
- Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.Journal of virology · 2026Article
- GC content mismatch of transgene destabilizes RNA virus genomes.Journal of virology · 2026Article
- Coronavirus NSP14 drives internal m7G modification to rewire host splicing and promote viral replication.Nucleic acids research · 2026Article
- Selective targeting of human TREX1 exonuclease by small molecule inhibitors is mediated by a conformational switch.NAR molecular medicine · 2026Article
- Synergistic antiviral effects of structure-guided peptides and a mutagenic base analog on SARS-CoV-2 replication.Antimicrobial agents and chemotherapy · 2026Article
- Targeting SARS-CoV-2 Non-Structural Proteins: A Blueprint for Next-Generation Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Slow PPThe Journal of biological chemistry · 2026Article
- RNA with Azvudine Incorporated One Nucleotide Upstream of 3'-End Resists Cleavage by SARS-CoV-2 Proofreading Exonuclease.Research square · 2026Article
- Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.bioRxiv : the preprint server for biology · 2026Article
- Inhibition of coronaviral exoribonuclease activity by TRIM-mediated SUMOylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Impact of mutations affecting 4'-fluorouridine susceptibility on fitness and treatment outcomes for Venezuelan equine encephalitis virus.Journal of virology · 2026Article
- Metal ions govern coronavirus endoribonuclease activity.Nucleic acids research · 2026Article
- Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals.Nature communications · 2026Article
- Inhibitory effects of molnupiravir on Crimean-Congo hemorrhagic fever virus polymerase.NAR molecular medicine · 2026Article
- Rethinking viral evolution: How BIAS mechanisms and Gamma-Poisson overdispersion redefine lethal mutagenesis.Frontiers in microbiology · 2026Article
- Shared quasispecies architecture in experimental and natural RNA virus populations.Virus evolution · 2026Article
- Structural and catalytic diversity of coronavirus proofreading exoribonuclease.Nature communications · 2025Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
High-fidelity replication of the large RNA genome of coronaviruses (CoVs) is mediated by a 3'-to-5' exoribonuclease (ExoN) in nonstructural protein 14 (nsp14), which excises nucleotides including antiviral drugs misincorporated by the low-fidelity viral RNA-dependent RNA polymerase (RdRp) and has also been implicated in viral RNA recombination and resistance to innate immunity. Here, we determined a 1.6-Å resolution crystal structure of severe acute respiratory syndrome CoV 2 (SARS-CoV-2) ExoN in complex with its essential cofactor, nsp10. The structure shows a highly basic and concave surface flanking the active site, comprising several Lys residues of nsp14 and the N-terminal amino group of nsp10. Modeling suggests that this basic patch binds to the template strand of double-stranded RNA substrates to position the 3' end of the nascent strand in the ExoN active site, which is corroborated by mutational and computational analyses. We also show that the ExoN activity can rescue a stalled RNA primer poisoned with sofosbuvir and allow RdRp to continue its extension in the presence of the chain-terminating drug, biochemically recapitulating proofreading in SARS-CoV-2 replication. Molecular dynamics simulations further show remarkable flexibility of multidomain nsp14 and suggest that nsp10 stabilizes ExoN for substrate RNA binding to support its exonuclease activity. Our high-resolution structure of the SARS-CoV-2 ExoN-nsp10 complex serves as a platform for future development of anticoronaviral drugs or strategies to attenuate the viral virulence.
Indexed as
Identifiers
What OpenQuestion holds
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.