Small molecule inhibitors of HCV replication from Pomegranate

Reddy, Uma B and Mullick, Ranajoy and Kumar, Anuj and Sudha, Govindarajan and Srinivasan, Narayanaswamy and Das, Saumitra (2014) Small molecule inhibitors of HCV replication from Pomegranate. In: SCIENTIFIC REPORTS, 4 .

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Abstract

Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and `no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

Item Type:	Journal Article
Publication:	SCIENTIFIC REPORTS
Publisher:	NATURE PUBLISHING GROUP
Additional Information:	Copyright for this article belongs to the NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	14 Aug 2014 09:49
Last Modified:	14 Aug 2014 09:49
URI:	http://eprints.iisc.ac.in/id/eprint/49543

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