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Viruses 2010, 2(8), 1752-1765; doi:10.3390/v2081752

Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel

Institut de Recherche en Immunologie et en Cancérologie (IRIC), Montréal, Québec, H3T 1J4, Canada
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Received: 3 June 2010 / Revised: 12 August 2010 / Accepted: 18 August 2010 / Published: 20 August 2010
(This article belongs to the Special Issue Antivirals Against Hepatitis C Virus)
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Abstract

Hepatitis C virus (HCV) infection is a serious and growing threat to human health. The current treatment provides limited efficacy and is poorly tolerated, highlighting the urgent medical need for novel therapeutics. The membrane-targeted NS3 protein in complex with the NS4A comprises a serine protease domain (NS3/4A protease) that is essential for viral polyprotein maturation and contributes to the evasion of the host innate antiviral immunity by HCV. Therefore, the NS3/4A protease represents an attractive target for drug discovery, which is tied in with the challenge to develop selective small-molecule inhibitors. A rational drug design approach, based on the discovery of N-terminus product inhibition, led to the identification of potent and orally bioavailable NS3 inhibitors that target the highly conserved protease active site. This review summarizes the NS3 protease inhibitors currently challenged in clinical trials as one of the most promising antiviral drug class, and possibly among the first anti-HCV agents to be approved for the treatment of HCV infection. View Full-Text
Keywords: HCV; protease inhibitor; NS3 protease; antiviral therapy; HCV replicon; clinical trial HCV; protease inhibitor; NS3 protease; antiviral therapy; HCV replicon; clinical trial
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MDPI and ACS Style

Chatel-Chaix, L.; Baril, M.; Lamarre, D. Hepatitis C Virus NS3/4A Protease Inhibitors: A Light at the End of the Tunnel. Viruses 2010, 2, 1752-1765.

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