ArticleHepatology (Baltimore, Md.)2014
Structure-guided design affirms inhibitors of hepatitis C virus p7 as a viable class of antivirals targeting virion release.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
31 citing papers in PubMed, 62 citations in OpenAlex.
- Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins.Viruses · 2025Review
- Article
- Protein-driven membrane remodeling: Molecular perspectives from Flaviviridae infections.Biophysical journal · 2023Review
- SPCS1-Dependent E2-p7 processing determines HCV Assembly efficiency.PLoS pathogens · 2022Article
- Article
- Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza.PLoS pathogens · 2020Article
- Hepatitis C virus sequence divergence preserves p7 viroporin structural and dynamic features.Scientific reports · 2019Article
- Biological Function and Application of Picornaviral 2B Protein: A New Target for Antiviral Drug Development.Viruses · 2019Review
- Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation.PLoS pathogens · 2019Article
- Discovery and characterization of a novel HCV inhibitor targeting the late stage of HCV life cycle.Antiviral therapy · 2019Article
- Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.Chemical reviews · 2018Review
- The Unusual Transmembrane Partition of the Hexameric Channel of the Hepatitis C Virus.Structure (London, England : 1993) · 2018Article
- Symmetric dimeric adamantanes for exploring the structure of two viroporins: influenza virus M2 and hepatitis C virus p7.Drug design, development and therapy · 2018Article
- The amino-terminus of the hepatitis C virus (HCV) p7 viroporin and its cleavage from glycoprotein E2-p7 precursor determine specific infectivity and secretion levels of HCV particle types.PLoS pathogens · 2017Article
- Coupling neutron reflectivity with cell-free protein synthesis to probe membrane protein structure in supported bilayers.Scientific reports · 2017Article
- Current therapy for chronic hepatitis C: The role of direct-acting antivirals.Antiviral research · 2017Review
- Viral channel forming proteins--How to assemble and depolarize lipid membranes in silico.Biochimica et biophysica acta · 2016Review
- Ion Channel Function and Cross-Species Determinants in Viral Assembly of Nonprimate Hepacivirus p7.Journal of virology · 2016Article
- Structural basis of interaction between the hepatitis C virus p7 channel and its blocker hexamethylene amiloride.Protein & cell · 2016Article
- Targeting the Channel Activity of Viroporins.Advances in protein chemistry and structural biology · 2016Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledCurrent interferon-based therapy for hepatitis C virus (HCV) infection is inadequate, prompting a shift toward combinations of direct-acting antivirals (DAA) with the first protease-targeted drugs licensed in 2012. Many compounds are in the pipeline yet primarily target only three viral proteins, namely, NS3/4A protease, NS5B polymerase, and NS5A. With concerns growing over resistance, broadening the repertoire for DAA targets is a major priority. Here we describe the complete structure of the HCV p7 protein as a monomeric hairpin, solved using a novel combination of chemical shift and nuclear Overhauser effect (NOE)-based methods. This represents atomic resolution information for a full-length virus-coded ion channel, or "viroporin," whose essential functions represent a clinically proven class of antiviral target exploited previously for influenza A virus therapy. Specific drug-protein interactions validate an allosteric site on the channel periphery and its relevance is demonstrated by the selection of novel, structurally diverse inhibitory small molecules with nanomolar potency in culture. Hit compounds represent a 10,000-fold improvement over prototypes, suppress rimantadine resistance polymorphisms at submicromolar concentrations, and show activity against other HCV genotypes.
conclusionThis proof-of-principle that structure-guided design can lead to drug-like molecules affirms p7 as a much-needed new target in the burgeoning era of HCV DAA.
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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.