Amiodarone inhibits the entry and assembly steps of Hepatitis C virus life cycle

Hepatitis C virus infection affects an estimated 180 million people in the world’s population. Adverse effects occurred frequently with current standard treatment of interferon and ribavirin, while resistance of new direct anti-viral agents, NS3 protease inhibitors, is a major concern due to 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 shown to inhibit hepatitis C virus infection in vitro. The detail mechanism has yet been clarified. The current study was to elucidate the molecular mechanism of 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 cell culture-derived HCV (HCVcc), HCV pseudoviral particles (HCVpp), sub-genomic replicons, internal ribosomal entry site (IRES)-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 HCV assembly step, via the suppression of microsomal triglyceride transfer protein (MTP) activity. Amiodarone revealed no effects on HCV replication and translation. With the host factor-targeting characteristics, amiodarone may be an attractive agent for treatment of HCV infection.
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research