A natural small molecule inhibitor corilagin blocks HCV replication and modulates oxidative stress to reduce liver damage

Antiviral Res. 2018 Feb;150:47-59. doi: 10.1016/j.antiviral.2017.12.004. Epub 2017 Dec 7.


Hepatitis C virus (HCV) infection causes chronic liver disease, which often leads to hepatocellular carcinoma. Earlier, we have demonstrated anti-HCV property of the methanolic extract of Phyllanthus amarus, an age-old folk-medicine against viral hepatitis. Here, we report identification of a principal bioactive component 'corilagin', which showed significant inhibition of the HCV key enzymes, NS3 protease and NS5B RNA-dependent-RNA-polymerase. This pure compound could effectively inhibit viral replication in the infectious cell culture system, displayed strong antioxidant activity by blocking HCV induced generation of reactive oxygen species and suppressed up-regulation of NOX4 and TGF-β mRNA levels. Oral administration of corilagin in BALB/c mice demonstrated its better tolerability and systemic bioavailability. More importantly, corilagin could restrict serum HCV RNA levels, decrease collagen deposition and hepatic cell denaturation in HCV infected chimeric mice harbouring human hepatocytes. Taken together, results provide a basis towards developing a pure natural drug as an alternate therapeutic strategy for restricting viral replication and prevent liver damage towards better management of HCV induced pathogenesis.

Keywords: Antiviral; Hepatitis C virus; Oxidative stress; Small molecule inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression
  • Genes, Reporter
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Hepacivirus / drug effects*
  • Hepacivirus / physiology*
  • Hepatitis C / complications
  • Hepatitis C / metabolism*
  • Hepatitis C / pathology
  • Hepatitis C / virology*
  • Humans
  • Hydrolyzable Tannins / isolation & purification
  • Hydrolyzable Tannins / pharmacology*
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / virology*
  • Liver Cirrhosis
  • Mice
  • NADPH Oxidase 4 / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / metabolism
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / metabolism
  • Virus Replication / drug effects


  • Antiviral Agents
  • Glucosides
  • Hydrolyzable Tannins
  • NS3 protein, hepatitis C virus
  • NS4 protein, hepatitis C virus
  • Plant Extracts
  • Reactive Oxygen Species
  • Transforming Growth Factor beta
  • Viral Nonstructural Proteins
  • corilagin
  • NADPH Oxidase 4
  • NOX4 protein, human