Inhibition of the Interaction Between NS3 Protease and HCV IRES With a Small Peptide: A Novel Therapeutic Strategy

Ray, Upasana and Roy, Chaitrali L and Kumar, Anuj and Mani, Prashant and Joseph, Agnel P and Sudha, G and Sarkar, Debi P and Srinivasan, N and Das, Saumitra (2013) Inhibition of the Interaction Between NS3 Protease and HCV IRES With a Small Peptide: A Novel Therapeutic Strategy. In: MOLECULAR THERAPY, 21 (1). pp. 57-67.

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Abstract

Recently, we have demonstrated that the protease domain of NS3 alone can bind specifically to hepatitis C virus (HCV) internal ribosome entry site (IRES) near the initiator AUG, dislodges human La protein and inhibits translation in favor of viral RNA replication. Here, by using a computational approach, the contact points of the protease on the HCV IRES were putatively mapped. A 30-mer NS3 peptide was designed from the predicted RNA-binding region that retained RNA-binding ability and also inhibited IRES-mediated translation. This peptide was truncated to 15 mer and this also demonstrated ability to inhibit HCV RNA-directed translation as well as replication. More importantly, its activity was tested in an in vivo mouse model by encapsulating the peptide in Sendai virus virosomes followed by intravenous delivery. The study demonstrates for the first time that the HCV NS3-IRES RNA interaction can be selectively inhibited using a small peptide and reports a strategy to deliver the peptide into the liver.

Item Type:	Journal Article
Publication:	MOLECULAR THERAPY
Publisher:	NATURE PUBLISHING GROUP
Additional Information:	Copy right for this article belongs to NATURE PUBLISHING GROUP, NEW YORK
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	06 Feb 2013 12:19
Last Modified:	06 Feb 2013 12:19
URI:	http://eprints.iisc.ac.in/id/eprint/45724

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