title: Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection.
abstract: Arbidol (ARB) is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV) infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 microM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.
authors.affiliation: Departments of Laboratory Medicine, Microbiology and Pathobiology, University of Washington, Seattle, USA. yboriskin@gmail.com
authors.forename: Yury S
authors.initials: YS
authors.lastname: Boriskin
authors.forename: Eve-Isabelle
authors.initials: EI
authors.lastname: Pécheur
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Polyak
mesh_terms: D000208:Acute Disease; D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008561:Membrane Fusion / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D013440:Sulfides
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D016899:Interferon-beta; D012367:RNA, Viral; D018168:Receptors, Retinoic Acid; C437968:PLAAT4 protein, human; C086979:umifenovir; D013440:Sulfides