Literature DB >> 21513964

The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein.

Choongho Lee1, Han Ma, Julie Qi Hang, Vincent Leveque, Ella H Sklan, Menashe Elazar, Klaus Klumpp, Jeffrey S Glenn.   

Abstract

The hepatitis C virus (HCV) non-structural (NS) 5A protein plays an essential role in the replication of the viral RNA by the membrane-associated replication complex (RC). Recently, a putative NS5A inhibitor, BMS-790052, exhibited the highest potency of any known anti-HCV compound in inhibiting HCV replication in vitro and showed a promising clinical effect in HCV-infected patients. The precise mechanism of action for this new class of potential anti-HCV therapeutics, however, is still unclear. In order to gain further insight into its mode of action, we sought to test the hypothesis that the antiviral effect of BMS-790052 might be mediated by interfering with the functional assembly of the HCV RC. We observed that BMS-790052 indeed altered the subcellular localization and biochemical fractionation of NS5A. Taken together, our data suggest that NS5A inhibitors such as BMS-790052 can suppress viral genome replication by altering the proper localization of NS5A into functional RCs.
Copyright © 2011 Elsevier Inc. All rights reserved.

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Year:  2011        PMID: 21513964      PMCID: PMC3096933          DOI: 10.1016/j.virol.2011.03.026

Source DB:  PubMed          Journal:  Virology        ISSN: 0042-6822            Impact factor:   3.616


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