April 22, 2013

NS5A Inhibitors in the Treatment of Hepatitis C

Journal of Hepatology

Jean-Michel Pawlotsky

Corresponding author. Department of Virology, Hôpital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. Tel.: +33 1 4981 2827.

Received 28 February 2013; received in revised form 22 March 2013; accepted 27 March 2013. published online 08 April 2013.
Accepted Manuscript

Article in Press

Abstract

Hepatitis C virus infection is a major health problem worldwide and no vaccine has yet been developed against this virus. In addition, currently approved pharmacotherapies achieve suboptimal cure rates and have side effects that result in noncompliance and premature treatment discontinuation. Significant research has been devoted to developing direct-acting antiviral agents that inhibit key viral functions. In particular, several novel drug candidates that inhibit the viral nonstructural protein 5A (NS5A) have been demonstrated to possess high potency, pan-genotypic activity, and a high barrier to resistance. Clinical trials using combination therapies containing NS5A inhibitors have reported results that promise high cure rates and raise the possibility of developing interferon-free, all-oral regimens.

Abbreviations: HCV, hepatitis C virus, DAA, direct acting antiviral, NS, nonstructural, RdRp, RNA-dependent RNA polymerase, IFN, interferon, UTR, untranslated region, IRES, internal ribosome entry site, SVR, sustained virological response, RVR, rapid virologic response, cEVR, complete early virologic response

Keywords: Hepatitis C virus, NS5A inhibitor, Daclatasvir, Resistance

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