ArticleCommunications biology2021
Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 132 citations in OpenAlex.
- Hitting Coronaviruses Where It Hurts: Antiviral Strategies Targeting Viral Proteins.ChemMedChem · 2026Review
- Coronavirus Nsp15 endoribonuclease: linking viral RNA regulation to immune evasion and viral fitness.Journal of virology · 2026Review
- Identification of Nsp15 inhibitors restoring interferon-dependent antiviral activity against SARS-CoV-2.Antiviral research · 2026Article
- Targeting SARS-CoV-2 Non-Structural Proteins: A Blueprint for Next-Generation Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Metal ions govern coronavirus endoribonuclease activity.Nucleic acids research · 2026Article
- SARS-CoV-2 nsp15 enhances viral virulence by subverting host antiviral defenses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional implications of hexameric dynamics in SARS-CoV-2 Nsp15.Protein science : a publication of the Protein Society · 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
- Identification of acrylamide-based covalent inhibitors of SARS-CoV-2 (SCoV-2) Nsp15 using high-throughput screening and machine learning.RSC advances · 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
- A guanidine-based coronavirus replication inhibitor which targets the nsp15 endoribonuclease and selects for interferon-susceptible mutant viruses.PLoS pathogens · 2025Article
- Spontaneous base flipping helps drive Nsp15's preferences in double stranded RNA substrates.Nature communications · 2025Article
- Immuno-epigenetic paradigms in coronavirus infection.Frontiers in immunology · 2025Review
- Thymidine phosphorylase mediates SARS-CoV-2 spike protein enhanced thrombosis in K18-hACE2Thrombosis research · 2024Article
- Alternative substrate kinetics of SARS-CoV-2 Nsp15 endonuclease reveals a specificity landscape dominated by RNA structure.Nucleic acids research · 2024Article
- Structural insights into RNA cleavage by a novel family of bacterial RNases.Nucleic acids research · 2024Article
- COVID-19 drug discovery and treatment options.Nature reviews. Microbiology · 2024Review
- Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15.Protein & cell · 2024Article
- Cracking the Code: Enhancing Molecular Tools for Progress in Nanobiotechnology.ACS applied bio materials · 2024Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
SARS-CoV-2 Nsp15 is a uridine-specific endoribonuclease with C-terminal catalytic domain belonging to the EndoU family that is highly conserved in coronaviruses. As endoribonuclease activity seems to be responsible for the interference with the innate immune response, Nsp15 emerges as an attractive target for therapeutic intervention. Here we report the first structures with bound nucleotides and show how the enzyme specifically recognizes uridine moiety. In addition to a uridine site we present evidence for a second base binding site that can accommodate any base. The structure with a transition state analog, uridine vanadate, confirms interactions key to catalytic mechanisms. In the presence of manganese ions, the enzyme cleaves unpaired RNAs. This acquired knowledge was instrumental in identifying Tipiracil, an FDA approved drug that is used in the treatment of colorectal cancer, as a potential anti-COVID-19 drug. Using crystallography, biochemical, and whole-cell assays, we demonstrate that Tipiracil inhibits SARS-CoV-2 Nsp15 by interacting with the uridine binding pocket in the enzyme's active site. Our findings provide new insights for the development of uracil scaffold-based drugs.
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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.