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

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

Author information

1
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.
2
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.
3
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India. Electronic address: sdas@iisc.ac.in.

Abstract

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

PMID:
29224736
DOI:
10.1016/j.antiviral.2017.12.004
[Indexed for MEDLINE]

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