Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity

J Viral Hepat. 2012 Feb;19(2):e81-8. doi: 10.1111/j.1365-2893.2011.01507.x. Epub 2011 Aug 16.


Phytochemicals exert antiviral activity and may play a potential therapeutic role in hepatitis C virus (HCV) infection. In this work, we aimed to isolate NS3 inhibitors from traditional Indian medicinal plants that were found, in our earlier study, to inhibit HCV NS3 protease activity and to evaluate their potential to inhibit HCV replication. A potent inhibitory effect of NS3 catalytic activity was obtained with Embelia ribes plant extracts. Quercetin, a ubiquitous plant flavonoid, was identified as the active substance in the fractioned extract. It was found to inhibit NS3 activity in a specific dose-dependent manner in an in vitro catalysis assay. Quercetin inhibited HCV RNA replication as analysed in the subgenomic HCV RNA replicon system. It also inhibited HCV infectious virus production in the HCV infectious cell culture system (HCVcc), as analysed by the focus-forming unit reduction assay and HCV RNA real-time PCR. The inhibitory effect of quercetin was also obtained when using a model system in which NS3 engineered substrates were introduced in NS3-expressing cells, providing evidence that inhibition in vivo could be directed to the NS3 and do not involve other HCV proteins. Our work demonstrates that quercetin has a direct inhibitory effect on the HCV NS3 protease. These results point to the potential of quercetin as a natural nontoxic anti-HCV agent reducing viral production by inhibiting both NS3 and heat shock proteins essential for HCV replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Embelia / chemistry
  • Hepacivirus / drug effects*
  • Hepacivirus / growth & development
  • Humans
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Protease Inhibitors / isolation & purification
  • Protease Inhibitors / pharmacology*
  • Quercetin / isolation & purification
  • Quercetin / pharmacology*
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • Real-Time Polymerase Chain Reaction
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Virus Replication / drug effects


  • Antiviral Agents
  • NS3 protein, hepatitis C virus
  • Plant Extracts
  • Protease Inhibitors
  • RNA, Viral
  • Viral Nonstructural Proteins
  • Quercetin