ArticleNucleic acids research2022
Flipped over U: structural basis for dsRNA cleavage by the SARS-CoV-2 endoribonuclease.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- Coronavirus Nsp15 endoribonuclease: linking viral RNA regulation to immune evasion and viral fitness.Journal of virology · 2026Review
- A combined PIE-FRET and FCS assay to monitor RNA dynamics and cleavage by SARS-CoV-2 Nsp15.Scientific reports · 2026Article
- PKR condensation at viral replication complexes initiates its activation.Cell reports · 2026Article
- Metal ions govern coronavirus endoribonuclease activity.Nucleic acids research · 2026Article
- SARS-CoV-2 EndoU-ribonuclease regulates RNA recombination and impacts viral fitness.Nature communications · 2025Article
- Cleavage sequence specificity of Nsp15.RNA biology · 2025Article
- A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription.Journal of virology · 2025Article
- A combined PIE-FRET and FCS assay to monitor RNA dynamics and cleavage by SARS-CoV-2 Nsp15.Research square · 2025Article
- SARS-CoV-2 Nsp15 endoribonuclease subverts host defenses to enhance viral fitness in lung cells.Journal of virology · 2025Article
- Structural heterogeneity and dynamics in the apical stem loop of s2m from SARS-CoV-2 Delta by an integrative NMR spectroscopy and MD simulation approach.Nucleic acids research · 2025Article
- 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
- 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
- Functional implications of hexameric dynamics in SARS-CoV-2 Nsp15.Protein science : a publication of the Protein Society · 2025Article
- Identification of acrylamide-based covalent inhibitors of SARS-CoV-2 (SCoV-2) Nsp15 using high-throughput screening and machine learning.RSC advances · 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
- MDA5 Is a Major Determinant of Developing Symptoms in Critically Ill COVID-19 Patients.Clinical reviews in allergy & immunology · 2024Review
- Alternative substrate kinetics of SARS-CoV-2 Nsp15 endonuclease reveals a specificity landscape dominated by RNA structure.Nucleic acids research · 2024Article
- IBR1, a novel endogenous IFIH1-binding dsRNA, governs IFIH1 activation and M1 macrophage polarisation in ARDS.Clinical and translational medicine · 2024Article
- Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15.Protein & cell · 2024Article
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7 authors at 1 institution in 1 country.
Funding
Abstract
Coronaviruses generate double-stranded (ds) RNA intermediates during viral replication that can activate host immune sensors. To evade activation of the host pattern recognition receptor MDA5, coronaviruses employ Nsp15, which is a uridine-specific endoribonuclease. Nsp15 is proposed to associate with the coronavirus replication-transcription complex within double-membrane vesicles to cleave these dsRNA intermediates. How Nsp15 recognizes and processes dsRNA is poorly understood because previous structural studies of Nsp15 have been limited to small single-stranded (ss) RNA substrates. Here we present cryo-EM structures of SARS-CoV-2 Nsp15 bound to a 52nt dsRNA. We observed that the Nsp15 hexamer forms a platform for engaging dsRNA across multiple protomers. The structures, along with site-directed mutagenesis and RNA cleavage assays revealed critical insight into dsRNA recognition and processing. To process dsRNA Nsp15 utilizes a base-flipping mechanism to properly orient the uridine within the active site for cleavage. Our findings show that Nsp15 is a distinctive endoribonuclease that can cleave both ss- and dsRNA effectively.
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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.