Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection.
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.
Boriskin
Yury S
YS
Departments of Laboratory Medicine, Microbiology and Pathobiology, University of Washington, Seattle, USA. yboriskin@gmail.com
Pécheur
Eve-Isabelle
EI
Polyak
Stephen J
SJ
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
D000998:Antiviral Agents; D007211:Indoles; D016899:Interferon-beta; D012367:RNA, Viral; D018168:Receptors, Retinoic Acid; C437968:PLAAT4 protein, human; C086979:umifenovir; D013440:Sulfides