ArticleProceedings of the National Academy of Sciences of the United States of America2004
Major genetic marker of nidoviruses encodes a replicative endoribonuclease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers.
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Who cites it
210 citing papers in PubMed, 300 citations in OpenAlex.
- Coronavirus Nsp15 endoribonuclease: linking viral RNA regulation to immune evasion and viral fitness.Journal of virology · 2026Review
- Metal ions govern coronavirus endoribonuclease activity.Nucleic acids research · 2026Article
- Pharmacophores of Influenza Virus PA Endonuclease Inhibitors.Advances in experimental medicine and biology · 2026Review
- TRIM29 inhibits PRRSV replication by targeting nsp11 for degradation.Journal of virology · 2025Article
- Infectious Bronchitis Virus Activates the Aryl Hydrocarbon Receptor During In Vitro Infection.Veterinary sciences · 2025Article
- Identification, validation, and characterization of approved and investigational drugs interfering with the SARS-CoV-2 endoribonuclease Nsp15.Protein science : a publication of the Protein Society · 2025Article
- Molecular basis for the calcium-dependent activation of the ribonuclease EndoU.Nature communications · 2025Article
- Coronavirus endoribonuclease antagonizes ZBP1-mediated necroptosis and delays multiple cell death pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Coronavirus endoribonuclease nsp15 suppresses host protein synthesis and evades PKR-eIF2α-mediated translation shutoff to ensure viral protein synthesis.PLoS pathogens · 2025Article
- Discovery of small molecules against porcine reproductive and respiratory syndrome virus replication by targeting NendoU activity.Journal of virology · 2025Article
- Article
- A guanidine-based coronavirus replication inhibitor which targets the nsp15 endoribonuclease and selects for interferon-susceptible mutant viruses.PLoS pathogens · 2025Article
- Screening of RNA methyltransferase NSP16 inhibitors against SARS-CoV-2 coronavirus and study of related mechanisms.American journal of translational research · 2025Article
- Alternative substrate kinetics of SARS-CoV-2 Nsp15 endonuclease reveals a specificity landscape dominated by RNA structure.Nucleic acids research · 2024Article
- Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15.Protein & cell · 2024Article
- SARS-CoV-2 nsp15 preferentially degrades AU-rich dsRNA via its dsRNA nickase activity.Nucleic acids research · 2024Article
- Inhibition of SARS-CoV-2 NSP-15 by Uridine-5'-Monophosphate Analogues Using QSAR Modelling, Molecular Dynamics Simulations, and Free Energy Landscape.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15.bioRxiv : the preprint server for biology · 2023Article
- The endoribonuclease Arlr is required to maintain lipid homeostasis by downregulating lipolytic genes during aging.Nature communications · 2023Article
- Atovaquone and Pibrentasvir Inhibit the SARS-CoV-2 Endoribonuclease and Restrict Infection In Vitro but Not In Vivo.Viruses · 2023Article
150 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coronaviruses are important pathogens that cause acute respiratory diseases in humans. Replication of the approximately 30-kb positive-strand RNA genome of coronaviruses and discontinuous synthesis of an extensive set of subgenome-length RNAs (transcription) are mediated by the replicase-transcriptase, a barely characterized protein complex that comprises several cellular proteins and up to 16 viral subunits. The coronavirus replicase-transcriptase was recently predicted to contain RNA-processing enzymes that are extremely rare or absent in other RNA viruses. Here, we established and characterized the activity of one of these enzymes, replicative nidoviral uridylate-specific endoribonuclease (NendoU). It is considered a major genetic marker that discriminates nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) from all other RNA virus families. Bacterially expressed forms of NendoU of severe acute respiratory syndrome coronavirus and human coronavirus 229E were revealed to cleave single-stranded and double-stranded RNA in a Mn(2+)-dependent manner. Single-stranded RNA was cleaved less specifically and effectively, suggesting that double-stranded RNA is the biologically relevant NendoU substrate. Double-stranded RNA substrates were cleaved upstream and downstream of uridylates at GUU or GU sequences to produce molecules with 2'-3' cyclic phosphate ends. 2'-O-ribose-methylated RNA substrates proved to be resistant to cleavage by NendoU, indicating a functional link with the 2'-O-ribose methyltransferase located adjacent to NendoU in the coronavirus replicative polyprotein. A mutagenesis study verified potential active-site residues and allowed us to inactivate NendoU in the full-length human coronavirus 229E clone. Substitution of D6408 by Ala was shown to abolish viral RNA synthesis, demonstrating that NendoU has critical functions in viral replication and transcription.
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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.