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

Reddy, B Uma and Mullick, Ranajoy and Kumar, Anuj and Sharma, Geetika and Bag, Paromita and Roy, Chaitrali Laha and Sudha, Govindarajan and Tandon, Himani and Dave, Pratik and Shukla, Ashutosh and Srinivasan, Priyanka and Nandhitha, Madhusudhan and Srinivasan, Narayanaswamy and Das, Saumitra (2018) A natural small molecule inhibitor corilagin blocks HCV replication and modulates oxidative stress to reduce liver damage. In: ANTIVIRAL RESEARCH, 150 . pp. 47-59.

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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-beta 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.

Item Type:	Journal Article
Publication:	ANTIVIRAL RESEARCH
Publisher:	ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Additional Information:	Copy right for the article belong to ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	08 Mar 2018 19:07
Last Modified:	08 Mar 2018 19:07
URI:	http://eprints.iisc.ac.in/id/eprint/59132

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