Suppression of hepatitis c virus genome replication and particle production by a novel diacylglycerol acyltransferases inhibitor

Dahee Kim, Ja Il Goo, Mi Il Kim, Sung Jin Lee, Moonju Choi, Thoa Thi Than, Phuong Hong Nguyen, Marc P. Windisch, Kyeong Lee, Yongseok Choi, Choongho Lee

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number2083
JournalMolecules
Volume23
Issue number8
DOIs
Publication statusPublished - 2018 Aug 20

Keywords

  • DGAT inhibitor
  • Diacylglycerol acyltransferase (DGAT)
  • HCV genome replication
  • HCV particle production
  • Hepatitis C virus (HCV)
  • Lipid droplet (LD)

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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  • Cite this

    Kim, D., Goo, J. I., Kim, M. I., Lee, S. J., Choi, M., Than, T. T., Nguyen, P. H., Windisch, M. P., Lee, K., Choi, Y., & Lee, C. (2018). Suppression of hepatitis c virus genome replication and particle production by a novel diacylglycerol acyltransferases inhibitor. Molecules, 23(8), [2083]. https://doi.org/10.3390/molecules23082083