ArticleThe Journal of infectious diseases2010
The hepatitis C virus (HCV) NS4B RNA binding inhibitor clemizole is highly synergistic with HCV protease inhibitors.
Article in The Journal of infectious diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 61 citations in OpenAlex.
- Article
- Donor-derived airway air-liquid interface model for high-throughput screening of antiviral combinations with concurrent analysis of antiviral efficacy and epithelial toxicity using ciliR.ERJ open research · 2026Article
- Anti-COVID-19 activity and simple HPLC method for concurrent detection of repurposed drugs in novel binary mixtures.AMB Express · 2026Article
- Novel Anti-Enterovirus A71 Compounds Discovered by Repositioning Antivirals from the Open-Source MMV Pandemic Response Box.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Inhibition of Human Coronaviruses by Combinations of Host-Targeted and Direct-Acting Antivirals.Antimicrobial agents and chemotherapy · 2023Article
- Favipiravir Inhibits Hepatitis A Virus Infection in Human Hepatocytes.International journal of molecular sciences · 2022Article
- Synergistic and Antagonistic Drug Combinations against SARS-CoV-2.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Discovery of Synergistic and Antagonistic Drug Combinations against SARS-CoV-2 In Vitro.bioRxiv : the preprint server for biology · 2020Article
- Replicons of a Rodent Hepatitis C Model Virus Permit Selection of Highly Permissive Cells.Journal of virology · 2019Article
- Review
- Clemizole hydrochloride blocks cardiac potassium currents stably expressed in HEK 293 cells.British journal of pharmacology · 2017Article
- Evaluation of antiviral drug synergy in an infectious HCV system.Antiviral therapy · 2016Article
- Flaviviral NS4b, chameleon and jack-in-the-box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention.Reviews in medical virology · 2015Review
- The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis.Critical reviews in microbiology · 2015Review
- AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate hepatitis C virus entry and are potential drug targets.Journal of virology · 2015Article
- A novel dengue virus inhibitor, BP13944, discovered by high-throughput screening with dengue virus replicon cells selects for resistance in the viral NS2B/NS3 protease.Antimicrobial agents and chemotherapy · 2014Article
- Using chimeric mice with humanized livers to predict human drug metabolism and a drug-drug interaction.The Journal of pharmacology and experimental therapeutics · 2013Article
- Antiviral drugs against hepatitis C virus.Genetic vaccines and therapy · 2011Article
- Mixing the right hepatitis C inhibitor cocktail.Trends in molecular medicine · 2011Review
- The Future of HCV Therapy: NS4B as an Antiviral Target.Viruses · 2010Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWe recently identified a compound, clemizole hydrochloride, that inhibits NS4B's RNA binding and hepatitis C virus (HCV) replication. Although significant, clemizole's antiviral effect is moderate (50% effective concentration of 8 microM against an HCV genotype 2a clone). We hypothesized that the combination of clemizole with other anti-HCV agents can increase the antiviral effect over that achieved with each drug alone and could also decrease the emergence of viral resistance.
methodsLuciferase reporter-linked HCV replication assays were used to study the antiviral effects of drug combinations that included clemizole. Data were analyzed using Loewe additivity and Bliss independence models for synergy, and resistance studies were performed using HCV colony formation assays.
resultsClemizole's antiviral effect was highly synergistic with the HCV protease inhibitors SCH503034 and VX950, without toxicity. In contrast, combinations of clemizole with either interferon, ribavirin, or the nucleoside (NM283) and nonnucleoside (HCV796) HCV polymerase inhibitors were additive. Furthermore, combination of clemizole with SCH503034 decreased the frequency of drug-resistant mutants, compared with treatment with either drug alone. Finally, no cross-resistance to clemizole of SCH503034-resistant mutants (or vice versa) was observed.
conclusionsClemizole can yield high-level synergy with the protease inhibitor class. Inclusion of clemizole in future anti-HCV cocktails can represent an attractive paradigm for increasing current virologic response rates.
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