ArticleScientific reports2022
Characterization of SARS-CoV-2 replication complex elongation and proofreading activity.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- SARS-CoV-2 resistance analyses from the Phase 3 PINETREE study of remdesivir treatment in nonhospitalized participants.Antimicrobial agents and chemotherapy · 2025Trial
- Mechanism of SARS-CoV-2 resistance to nucleotide analog-based antivirals.Nature communications · 2026Article
- SARS-CoV-2 intra-host evolution during acute infection in COVID-19 patients.Frontiers in microbiology · 2026Article
- Structural and catalytic diversity of coronavirus proofreading exoribonuclease.Nature communications · 2025Article
- Impact of an oxidative RNA lesion on in vitro replication catalyzed by SARS-CoV-2 RNA-dependent RNA polymerase.The Journal of biological chemistry · 2025Article
- A High-Throughput Screening Pipeline to Identify Methyltransferase and Exonuclease Inhibitors of SARS-CoV-2 NSP14.Biochemistry · 2025Article
- Biochemical characterization of naturally occurring mutations in SARS-CoV-2 RNA-dependent RNA polymerase.Protein science : a publication of the Protein Society · 2024Article
- Adenosine modifications impede SARS-CoV-2 RNA-dependent RNA transcription.RNA (New York, N.Y.) · 2024Article
- Despite the odds: formation of the SARS-CoV-2 methylation complex.Nucleic acids research · 2024Article
- Review
- Studying the intersection of nucleoside modifications and SARS-CoV-2 RNA-dependent RNA transcription using an in vitro reconstituted system.Methods in enzymology · 2024Article
- Interfering with nucleotide excision by the coronavirus 3'-to-5' exoribonuclease.Nucleic acids research · 2023Article
- Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase.Computational and structural biotechnology journal · 2023Review
- Recent review of COVID-19 management: diagnosis, treatment and vaccination.Pharmacological reports : PR · 2022Review
- Interfering with nucleotide excision by the coronavirus 3'-to-5' exoribonuclease.bioRxiv : the preprint server for biology · 2022Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The replication complex (RC) of SARS-CoV-2 was recently shown to be one of the fastest RNA-dependent RNA polymerases of any known coronavirus. With this rapid elongation, the RC is more prone to incorporate mismatches during elongation, resulting in a highly variable genomic sequence. Such mutations render the design of viral protein targets difficult, as drugs optimized for a given viral protein sequence can quickly become inefficient as the genomic sequence evolves. Here, we use biochemical experiments to characterize features of RNA template recognition and elongation fidelity of the SARS-CoV-2 RdRp, and the role of the exonuclease, nsp14. Our study highlights the 2'OH group of the RNA ribose as a critical component for RdRp template recognition and elongation. We show that RdRp fidelity is reduced in the presence of the 3' deoxy-terminator nucleotide 3'dATP, which promotes the incorporation of mismatched nucleotides (leading to U:C, U:G, U:U, C:U, and A:C base pairs). We find that the nsp10-nsp14 heterodimer is unable to degrade RNA products lacking free 2'OH or 3'OH ribose groups. Our results suggest the potential use of 3' deoxy-terminator nucleotides in RNA-derived oligonucleotide inhibitors as antivirals against SARS-CoV-2.
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