ArticleProceedings of the National Academy of Sciences of the United States of America2009
Functional screen reveals SARS coronavirus nonstructural protein nsp14 as a novel cap N7 methyltransferase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 312 papers.
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Who cites it
312 citing papers in PubMed, 473 citations in OpenAlex.
- Recovery of proofreading-impaired SARS-CoV-2 reveals a mutator phenotype and an ExoN activity threshold for viability.Journal of virology · 2026Article
- Structural and Mechanistic Perspectives on SARS-CoV-2 Nonstructural Protein 14-Mediated Cap Formation and Drug Discovery.Microorganisms · 2026Review
- Multi-antigen coronavirus vaccine induces potent and durable cross-protection against multiple SARS-CoV-2 variants.NPJ vaccines · 2026Article
- Coronavirus NSP14 drives internal m7G modification to rewire host splicing and promote viral replication.Nucleic acids research · 2026Article
- Fibrillarin-mediated 2'-O-methylation serves as a translation brake on uncapped enterovirus RNA.PLoS pathogens · 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
- Article
- Metabolic stress reveals widespread accumulation of cap-unmethylated RNAs.bioRxiv : the preprint server for biology · 2026Article
- SARS-CoV-2 nsp14 induces the mCommunications biology · 2025Article
- Structural and catalytic diversity of coronavirus proofreading exoribonuclease.Nature communications · 2025Article
- A Comprehensive View on the Mechanisms of Coronavirus Escaping Innate Immunity.Veterinary sciences · 2025Review
- SARS-CoV-2 and HCoV-OC43 regulate host m6A modification via activation of the mTORC1 signalling pathway to facilitate viral replication.Emerging microbes & infections · 2025Article
- Assay development and screening of inhibitors targeting the SARS-CoV-2 2'-O-methyltransferase NSP16.Pharmaceutical science advances · 2025Article
- Development of the coronavirus reverse genetic system: Core technology for pathogenesis mechanisms research and vaccine/drug development.Virulence · 2025Review
- SARS-CoV-2 NSP14 inhibitor exhibits potent antiviral activity and reverses NSP14-driven host modulation.Nature communications · 2025Article
- Discovery, Optimization, and Evaluation of Non-Nucleoside SARS-CoV-2 NSP14 Inhibitors.Journal of medicinal chemistry · 2025Article
- Discovery of Novel Isofunctional SARS-CoV‑2 NSP14 RNA Cap Methyltransferase Inhibitors by Structure-Based Virtual Screening.ACS medicinal chemistry letters · 2025Article
- Iron-sulfur clusters in SARS-CoV-2 exoribonuclease and methyltransferase complexes: relevance for viral genome proofreading and capping.Nature communications · 2025Article
- Discovery of SARS-CoV-2 Nsp14-Methyltransferase (MTase) Inhibitors by Harnessing Scaffold-Centric Exploration of the Ultra Large Chemical Space.ACS pharmacology & translational science · 2025Article
- Anti-interferon armamentarium of human coronaviruses.Cellular and molecular life sciences : CMLS · 2025Review
252 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The N7-methylguanosine (m7G) cap is the defining structural feature of eukaryotic mRNAs. Most eukaryotic viruses that replicate in the cytoplasm, including coronaviruses, have evolved strategies to cap their RNAs. In this report, we used a yeast genetic system to functionally screen for the cap-forming enzymes encoded by severe acute respiratory syndrome (SARS) coronavirus and identified the nonstructural protein (nsp) 14 of SARS coronavirus as a (guanine-N7)-methyltransferase (N7-MTase) in vivo in yeast cells and in vitro using purified enzymes and RNA substrates. Interestingly, coronavirus nsp14 was previously characterized as a 3'-to-5' exoribonuclease, and by mutational analysis, we mapped the N7-MTase domain to the carboxy-terminal part of nsp14 that shows features conserved with cellular N7-MTase in structure-based sequence alignment. The exoribonuclease active site was dispensable but the exoribonuclease domain was required for N7-MTase activity. Such combination of the 2 functional domains in coronavirus nsp14 suggests that it may represent a novel form of RNA-processing enzymes. Mutational analysis in a replicon system showed that the N7-MTase activity was important for SARS virus replication/transcription and can thus be used as an attractive drug target to develop antivirals for control of coronaviruses including the deadly SARS virus. Furthermore, the observation that the N7-MTase of RNA life could function in lieu of that in DNA life provides interesting evolutionary insight and practical possibilities in antiviral drug screening.
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