ArticleCell2022
A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors.
Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Advances in spatial omics for the analysis of prostate cancer.Analytical and bioanalytical chemistry · 2026Review
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- Thapsigargin suppresses porcine hemagglutinating encephalomyelitis virus replication by disrupting host energy metabolism.Virologica Sinica · 2025Article
- SARS-CoV-2 NSP14 inhibitor exhibits potent antiviral activity and reverses NSP14-driven host modulation.Nature communications · 2025Article
- Mutations in feline infectious peritonitis virus nonstructural protein 14/16 methyltransferase attenuate the pathogenicity of the virus in cats.Journal of virology · 2025Article
- Polypeptide encoded by the -1 PRF signal of SARS-CoV-2 controls multiple enzymatic activities of the viral NiRAN domain.NAR molecular medicine · 2025Article
- How Does Porcine Epidemic Diarrhea Virus Escape Host Innate Immunity?Pathogens (Basel, Switzerland) · 2025Review
- The mechanism for GTP-mediated RNA capping by the SARS-CoV-2 NiRAN domain remains unresolved.Cell · 2025Article
- Technological breakthroughs and advancements in the application of mRNA vaccines: a comprehensive exploration and future prospects.Frontiers in immunology · 2025Review
- Article
- Identification and Ranking of Binding Sites from Structural Ensembles: Application to SARS-CoV-2.Viruses · 2024Article
- Drupacine as a potent SARS-CoV-2 replication inhibitorBiosafety and health · 2024Article
- Mutations in nonstructural proteins essential for pathogenicity in SARS-CoV-2-infected mice.Journal of virology · 2024Article
- Inhibition of SARS-CoV-2 Nsp9 ssDNA-Binding Activity and Cytotoxic Effects on H838, H1975, and A549 Human Non-Small Cell Lung Cancer Cells: Exploring the Potential ofInternational journal of molecular sciences · 2024Article
- SARS-CoV-2 biology and host interactions.Nature reviews. Microbiology · 2024Review
- SHIFTR enables the unbiased identification of proteins bound to specific RNA regions in live cells.Nucleic acids research · 2024Article
- Bio-Chemoinformatics-Driven Analysis of nsp7 and nsp8 Mutations and Their Effects on Viral Replication Protein Complex Stability.Current issues in molecular biology · 2024Article
- A structural analysis of the nsp9 protein from the coronavirus MERS CoV reveals a conserved RNA binding interface.Proteins · 2024Article
- New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic.Frontiers in immunology · 2024Review
- Characteristics of SARS-CoV-2 Omicron BA.5 variants in Shanghai after ending the zero-COVID policy in December 2022: a clinical and genomic analysis.Frontiers in microbiology · 2024Article
Corrections and comments
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket" in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an "induce-and-lock" mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.
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