ArticleScientific reports2014
Potent hepatitis C inhibitors bind directly to NS5A and reduce its affinity for RNA.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 114 citations in OpenAlex.
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- AI-Driven Enhancements in Drug Screening and Optimization.Methods in molecular biology (Clifton, N.J.) · 2024Article
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- Sub-stoichiometric Modulation of Viral Targets-Potent Antiviral Agents That Exploit Target Vulnerability.ACS medicinal chemistry letters · 2023Article
- Mechanisms of Action of the Host-Targeting Agent Cyclosporin A and Direct-Acting Antiviral Agents against Hepatitis C Virus.Viruses · 2023Article
- Using Graph-Based Signatures to Guide Rational Antibody Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Microscale Thermophoresis as a Tool to Study Protein Interactions and Their Implication in Human Diseases.International journal of molecular sciences · 2022Review
- Systematic evaluation of computational tools to predict the effects of mutations on protein stability in the absence of experimental structures.Briefings in bioinformatics · 2022Article
- Repurposing of FDA-approved drugs as potential inhibitors of the SARS-CoV-2 main protease: Molecular insights into improved therapeutic discovery.Computers in biology and medicine · 2022Article
- mmCSM-NA: accurately predicting effects of single and multiple mutations on protein-nucleic acid binding affinity.NAR genomics and bioinformatics · 2021Article
- A Novel Small Molecule Inhibits Hepatitis C Virus Propagation in Cell Culture.Microbiology spectrum · 2021Article
- mmCSM-PPI: predicting the effects of multiple point mutations on protein-protein interactions.Nucleic acids research · 2021Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- ThermoMutDB: a thermodynamic database for missense mutations.Nucleic acids research · 2021Article
- DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations.Protein science : a publication of the Protein Society · 2021Article
- Distinguishing between PTEN clinical phenotypes through mutation analysis.Computational and structural biotechnology journal · 2021Article
- Detection of low-level HCV variants in DAA treated patients: comparison amongst three different NGS data analysis protocols.Virology journal · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) infection affects more than 170 million people. The high genetic variability of HCV and the rapid development of drug-resistant strains are driving the urgent search for new direct-acting antiviral agents. A new class of agents has recently been developed that are believed to target the HCV protein NS5A although precisely where they interact and how they affect function is unknown. Here we describe an in vitro assay based on microscale thermophoresis and demonstrate that two clinically relevant inhibitors bind tightly to NS5A domain 1 and inhibit RNA binding. Conversely, RNA binding inhibits compound binding. The compounds bind more weakly to known resistance mutants L31V and Y93H. The compounds do not affect NS5A dimerisation. We propose that current NS5A inhibitors act by favouring a dimeric structure of NS5A that does not bind RNA.
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