Identification of natural compounds extracted from crude drugs as novel inhibitors of hepatitis C virus

Biochem Biophys Res Commun. 2021 Aug 27;567:1-8. doi: 10.1016/j.bbrc.2021.06.022. Epub 2021 Jun 12.

Abstract

Natural product-derived crude drugs are expected to yield an abundance of new drugs to treat infectious diseases. Hepatitis C virus (HCV) is an oncogenic virus that significantly impacts public health. In this study, we sought to identify anti-HCV compounds in extracts of natural products. A total of 110 natural compounds extracted from several herbal medicine plants were examined for antiviral activity against HCV. Using a Huh7-mCherry-NLS-IPS reporter system for HCV infection, we first performed a rapid screening for anti-HCV compounds extracted from crude drugs. The compounds threo-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol (#106) and medioresinol (#110), which were extracted from Crataegus cuneate, exhibited anti-HCV activity and significantly inhibited HCV production in a dose-dependent manner. Analyses using HCV pseudoparticle and subgenomic replicon systems indicated that compounds #106 and #110 specifically inhibit HCV RNA replication but not viral entry or translation. Interestingly, compound #106 also inhibited the replication and production of hepatitis A virus. Our findings suggest that C. cuneate is a new source for novel anti-hepatitis virus drug development.

Keywords: Anti-HCV compound; Drug screening; HCV; HCV replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Biological Products / chemistry
  • Biological Products / pharmacology
  • Crataegus / chemistry
  • Hepacivirus / drug effects*
  • Hepacivirus / physiology
  • Hepatitis C / drug therapy*
  • Humans
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plants, Medicinal / chemistry
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Biological Products
  • Plant Extracts
  • crataegus extract