ArticleThe Biochemical journal2021
Identifying SARS-CoV-2 antiviral compounds by screening for small molecule inhibitors of nsp15 endoribonuclease.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
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Who cites it
28 citing papers in PubMed, 65 citations in OpenAlex.
- Coronavirus Nsp15 endoribonuclease: linking viral RNA regulation to immune evasion and viral fitness.Journal of virology · 2026Review
- A Data-Driven Approach for Interpretable and Efficient Predictive Modeling: A Case Study in SARS-CoV-2 Protease Inhibitor Discovery Through Feature Selection.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Motif V is an allosteric couple between the SARS-CoV-2 nsp13 nucleotide triphosphatase and helicase active sites.The Journal of biological chemistry · 2026Article
- A guanidine-based coronavirus replication inhibitor which targets the nsp15 endoribonuclease and selects for interferon-susceptible mutant viruses.PLoS pathogens · 2025Article
- Dynamic Combinatorial Chemistry Unveils Nsp10 Inhibitors with Antiviral Potential Against SARS-CoV-2.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Alternative substrate kinetics of SARS-CoV-2 Nsp15 endonuclease reveals a specificity landscape dominated by RNA structure.Nucleic acids research · 2024Article
- Aurora: a fluorescent deoxyribozyme for high-throughput screening.Nucleic acids research · 2024Article
- Targeting Ribonucleases with Small Molecules and Bifunctional Molecules.ACS chemical biology · 2023Review
- Atovaquone and Pibrentasvir Inhibit the SARS-CoV-2 Endoribonuclease and Restrict Infection In Vitro but Not In Vivo.Viruses · 2023Article
- Screening and identification of emodin as an EBV DNase inhibitor to prevent its biological functions.Virology journal · 2023Article
- Novel ciprofloxacin and norfloxacin-tetrazole hybrids as potential antibacterial and antiviral agents: TargetingJournal of molecular structure · 2023Article
- Room-temperature structural studies of SARS-CoV-2 protein NendoU with an X-ray free-electron laser.Structure (London, England : 1993) · 2023Article
- Recent insights into the structure and function of coronavirus ribonucleases.FEBS open bio · 2022Review
- Review
- A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases.Molecules (Basel, Switzerland) · 2022Article
- Synthesis, Structure-Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication.Molecules (Basel, Switzerland) · 2022Article
- Structural biology of SARS-CoV-2: open the door for novel therapies.Signal transduction and targeted therapy · 2022Review
- Natural Compound ZINC12899676 Reduces Porcine Epidemic Diarrhea Virus Replication by Inhibiting the Viral NTPase Activity.Frontiers in pharmacology · 2022Article
- Pharmaceutical Prospects of Curcuminoids for the Remedy of COVID-19: Truth or Myth.Frontiers in pharmacology · 2022Review
- Identification of SARS-CoV-2 inhibitors through phylogenetics and drug repurposing.Structural chemistry · 2022Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
SARS-CoV-2 is responsible for COVID-19, a human disease that has caused over 2 million deaths, stretched health systems to near-breaking point and endangered economies of countries and families around the world. Antiviral treatments to combat COVID-19 are currently lacking. Remdesivir, the only antiviral drug approved for the treatment of COVID-19, can affect disease severity, but better treatments are needed. SARS-CoV-2 encodes 16 non-structural proteins (nsp) that possess different enzymatic activities with important roles in viral genome replication, transcription and host immune evasion. One key aspect of host immune evasion is performed by the uridine-directed endoribonuclease activity of nsp15. Here we describe the expression and purification of nsp15 recombinant protein. We have developed biochemical assays to follow its activity, and we have found evidence for allosteric behaviour. We screened a custom chemical library of over 5000 compounds to identify nsp15 endoribonuclease inhibitors, and we identified and validated NSC95397 as an inhibitor of nsp15 endoribonuclease in vitro. Although NSC95397 did not inhibit SARS-CoV-2 growth in VERO E6 cells, further studies will be required to determine the effect of nsp15 inhibition on host immune evasion.
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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.