Suppression of Hepatitis C Virus Genome Replication and Particle Production by a Novel Diacylglycerol Acyltransferases Inhibitor

Abstract

Diacylglycerol acyltransferases (DGATs) play a critical role in the biosynthesis of endogenous triglycerides (TGs) and formation of lipid droplets (LDs) in the liver. In particular, one member of DGATs, DGAT-1 was reported to be an essential host factor for the efficient production of hepatitis C virus (HCV) particles. By utilizing our previously characterized three different groups of twelve DGAT inhibitors, we found that one of the DGAT inhibitors, a 2-((4-adamantylphenoxy) methyl)-N-(furan-2-ylmethyl)-1H-benzo[d]imidazole-5-carboxam (10j) is a potent suppressor of both HCV genome replication and particle production. 10j was able to induce inhibition of these two critical viral functions in a mutually separate manner. Abrogation of the viral genome replication by 10j led to a significant reduction in the viral protein expression as well. Interestingly, we found that its antiviral effect did not depend on the reduction of TG biosynthesis by 10j. This suggests that the inhibitory activity of 10j against DGATs may not be directly related with its antiviral action.

Complementary and Alternative Medicine for the Treatment of Hepatitis C Virus Infection

“…RT-PCR pointed out that quercetin inhibited messenger RNA (mRNA) production for HCV and diacylglycerol acyltransferase (DGAT) enzyme in the infected cells. DGAT enzyme is thought to facilitate the life cycle of the HCV particle (Kim et al 2018). Primary human hepatocyte cells were cultured and infected with the JFH1 HCV strain and quercetin 50 μM was supplied to the cultured cells.…”