title: Amiodarone inhibits the entry and assembly steps of hepatitis C virus life cycle.
abstract: HCV (hepatitis C virus) infection affects an estimated 180 million people in the world's population. Adverse effects occur frequently with current standard treatment of interferon and ribavirin, while resistance of new direct anti-viral agents, NS3 protease inhibitors, is a major concern because of their single anti-HCV mechanism against the viral factor. New anti-viral agents are needed to resolve the problems. Amiodarone, an anti-arrhythmic drug, has recently been shown to inhibit HCV infection in vitro. The detailed mechanism has yet to be clarified. The aim of the present study was to elucidate the molecular mechanism of the inhibitory effect of amiodarone on HCV life cycle. The effect of amiodarone on HCV life cycle was investigated in Huh-7.5.1 cells with HCVcc (cell culture-derived HCV), HCVpp (HCV pseudoviral particles), sub-genomic replicons, IRES (internal ribosomal entry site)-mediated translation assay, and intracellular and extracellular infectivity assays. The administration of amiodarone appeared to inhibit HCV entry independent of genotypes, which was attributed to the down-regulation of CD81 receptor expression. The inhibitory effect of amiodarone also manifested in the HCV assembly step, via the suppression of MTP (microsomal triacylglycerol transfer protein) activity. Amiodarone revealed no effects on HCV replication and translation. With the host factor-targeting characteristics, amiodarone may be an attractive agent for the treatment of HCV infection.
authors: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
authors: Yuan-Lung
authors: YL
authors: Cheng
authors: Keng-Hsueh
authors: KH
authors: Lan
authors: Wei-Ping
authors: WP
authors: Lee
authors: Szu-Han
authors: SH
authors: Tseng
authors: Li-Rong
authors: LR
authors: Hung
authors: Han-Chieh
authors: HC
authors: Lin
authors: Fa-Yauh
authors: FY
authors: Lee
authors: Shou-Dong
authors: SD
authors: Lee
authors: Keng-Hsin
authors: KH
authors: Lan
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016174:Hepacivirus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D060225:Tetraspanin 28 / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D000998:Antiviral Agents; D060225:Tetraspanin 28; D000638:Amiodarone