ArticleProceedings of the National Academy of Sciences of the United States of America2010
Inhibitor-induced structural change in the HCV IRES domain IIa RNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Comparative Evaluation of Explicit Solvent Models for RNA-Ligand Docking.Journal of chemical information and modeling · 2026Article
- Decoding the Structural Complexity of Viral RNAs with SHAPE to Guide Antiviral Therapeutics.Viruses · 2026Review
- The RNA promoter for pathogenic orthoflaviviruses replication is universal and serves as target for viral inhibition.PLoS pathogens · 2026Article
- RLDOCKScore: A Scoring Function for RNA-Ligand Docking and Small Molecule Virtual Screening.Journal of chemical theory and computation · 2025Article
- SMTRI: A deep learning-based web service for predicting small molecules that target miRNA-mRNA interactions.Molecular therapy. Nucleic acids · 2024Article
- SPRank─A Knowledge-Based Scoring Function for RNA-Ligand Pose Prediction and Virtual Screening.Journal of chemical theory and computation · 2024Article
- Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system.RSC medicinal chemistry · 2024Article
- Systematic detection of tertiary structural modules in large RNAs and RNP interfaces by Tb-seq.Nature communications · 2023Article
- SILCS-RNA: Toward a Structure-Based Drug Design Approach for Targeting RNAs with Small Molecules.Journal of chemical theory and computation · 2022Article
- Pharmacophore-Based Discovery of Viral RNA Conformational Modulators.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Incorporation and Utility of a Responsive Ribonucleoside Analogue in Probing the Conformation of a Viral RNA Motif by Fluorescence andChembiochem : a European journal of chemical biology · 2022Article
- RNA drug discovery: Conformational restriction enhances specific modulation of the T-box riboswitch function.Bioorganic & medicinal chemistry · 2020Article
- IRES-targeting small molecule inhibits enterovirus 71 replication via allosteric stabilization of a ternary complex.Nature communications · 2020Article
- Location specific annealing of miR-122 and other small RNAs defines an Hepatitis C Virus 5' UTR regulatory element with distinct impacts on virus translation and genome stability.Nucleic acids research · 2020Article
- The Role of the Liver-Specific microRNA, miRNA-122 in the HCV Replication Cycle.International journal of molecular sciences · 2020Review
- Face-time with TAR: Portraits of an HIV-1 RNA with diverse modes of effector recognition relevant for drug discovery.The Journal of biological chemistry · 2019Review
- HnRNP A1 Alters the Structure of a Conserved Enterovirus IRES Domain to Stimulate Viral Translation.Journal of molecular biology · 2017Article
- Advancing viral RNA structure prediction: measuring the thermodynamics of pyrimidine-rich internal loops.RNA (New York, N.Y.) · 2017Article
- Identification of Spermidine Binding Site in T-box Riboswitch Antiterminator RNA.Chemical biology & drug design · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Translation of the hepatitis C virus (HCV) RNA is initiated from a highly structured internal ribosomal entry site (IRES) in the 5' untranslated region (5' UTR) of the RNA genome. An important structural feature of the native RNA is an approximately 90 degrees helical bend localized to domain IIa that positions the apical loop of domain IIb of the IRES near the 40S ribosomal E-site to promote eIF2-GDP release, facilitating 80S ribosome assembly. We report here the NMR structure of a domain IIa construct in complex with a potent small-molecule inhibitor of HCV replication. Molecular dynamics refinement in explicit solvent and subsequent energetic analysis indicated that each inhibitor stereoisomer bound with comparable affinity and in an equivalent binding mode. The in silico analysis was substantiated by fluorescence-based assays showing that the relative binding free energies differed by only 0.7 kcal/mol. Binding of the inhibitor displaces key nucleotide residues within the bulge region, effecting a major conformational change that eliminates the bent RNA helical trajectory, providing a mechanism for the antiviral activity of this inhibitor class.
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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.