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

• Published in: Antiviral research Vol. 150; pp. 47 - 59
• Main Authors: Reddy, B. Uma, Mullick, Ranajoy, Kumar, Anuj, Sharma, Geetika, Bag, Paromita, Roy, Chaitrali Laha, Sudha, Govindarajan, Tandon, Himani, Dave, Pratik, Shukla, Ashutosh, Srinivasan, Priyanka, Nandhitha, Madhusudhan, Srinivasan, Narayanaswamy, Das, Saumitra
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2018
• Subjects: Antiviral; Hepatitis C virus; Oxidative stress; Small molecule inhibitor; Oxidative stress; Poly(A); JFH1; EGFP; Small molecule inhibitor; SVR; DAAs; NF-κB; OECD; RdRp; ROS; TGFβ; Antiviral; UMP; HCV; Hepatitis C virus; RIPA buffer; Huh 7; ERK
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2017.12.004

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. [Display omitted] •Corilagin from Phyllanthus amarus inhibits the key HCV enzymes, NS3 protease and NS5B RdRp in vitro.•Corilagin also inhibits HCV replication in the infectious cell culture system.•Corilagin could restrict viral titer and reduce collagen deposition in humanized chimeric PXB mice liver.•Corilagin suppresses the levels of NOX4 and modulate oxidative stress to reduce liver damage induced by HCV proteins.