ArticleHepatology (Baltimore, Md.)2016
Flunarizine prevents hepatitis C virus membrane fusion in a genotype-dependent manner by targeting the potential fusion peptide within E1.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 70 citations in OpenAlex.
- Flunarizine as a Candidate for Drug Repurposing Against Human Pathogenic Mammarenaviruses.Viruses · 2025Article
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- Structures of the Hepaci-, Pegi-, and Pestiviruses envelope proteins suggest a novel membrane fusion mechanism.PLoS biology · 2023Article
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- Sites of vulnerability in HCV E1E2 identified by comprehensive functional screening.Cell reports · 2022Article
- Structural Modifications and Biological Evaluations of Rift Valley Fever Virus Inhibitors Identified from Chemical Library Screening.ACS omega · 2022Article
- Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.Immunity · 2022Article
- Entry Inhibitors of Hepatitis C Virus.Advances in experimental medicine and biology · 2022Article
- Targeting non-structural proteins of Hepatitis C virus for predicting repurposed drugs using QSAR and machine learning approaches.Computational and structural biotechnology journal · 2022Article
- Small-Molecule Inhibition of Viral Fusion Glycoproteins.Annual review of virology · 2021Review
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- Identification of multipotent drugs for COVID-19 therapeutics with the evaluation of their SARS-CoV2 inhibitory activity.Computational and structural biotechnology journal · 2021Article
- Repurposing Screens of FDA-Approved Drugs Identify 29 Inhibitors of SARS-CoV-2.Journal of microbiology and biotechnology · 2020Article
- Fluoxazolevir inhibits hepatitis C virus infection in humanized chimeric mice by blocking viral membrane fusion.Nature microbiology · 2020Article
- Filovirus Antiviral Activity of Cationic Amphiphilic Drugs Is Associated with Lipophilicity and Ability To Induce Phospholipidosis.Antimicrobial agents and chemotherapy · 2020Article
- Chlorcyclizine Inhibits Viral Fusion of Hepatitis C Virus Entry by Directly Targeting HCV Envelope Glycoprotein 1.Cell chemical biology · 2020Article
- Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process.International journal of molecular sciences · 2020Review
- Hepatitis C Virus Entry: Protein Interactions and Fusion Determinants Governing Productive Hepatocyte Invasion.Cold Spring Harbor perspectives in medicine · 2020Review
- Flexibility and intrinsic disorder are conserved features of hepatitis C virus E2 glycoprotein.PLoS computational biology · 2020Article
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24 authors at 10 institutions in 4 countries.
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Abstract
unlabelledTo explore mechanisms of hepatitis C viral (HCV) replication we screened a compound library including licensed drugs. Flunarizine, a diphenylmethylpiperazine used to treat migraine, inhibited HCV cell entry in vitro and in vivo in a genotype-dependent fashion. Analysis of mosaic viruses between susceptible and resistant strains revealed that E1 and E2 glycoproteins confer susceptibility to flunarizine. Time of addition experiments and single particle tracking of HCV demonstrated that flunarizine specifically prevents membrane fusion. Related phenothiazines and pimozide also inhibited HCV infection and preferentially targeted HCV genotype 2 viruses. However, phenothiazines and pimozide exhibited improved genotype coverage including the difficult to treat genotype 3. Flunarizine-resistant HCV carried mutations within the alleged fusion peptide and displayed cross-resistance to these compounds, indicating that these drugs have a common mode of action.
conclusionThese observations reveal novel details about HCV membrane fusion; moreover, flunarizine and related compounds represent first-in-class HCV fusion inhibitors that merit consideration for repurposing as a cost-effective component of HCV combination therapies.
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