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J. Virol. doi:10.1128/JVI.02083-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Synergy of small molecular inhibitors of HCV replication directed at multiple viral targets

Department of Medicine, Division of Infectious Diseases, and Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, CA

^* To whom correspondence should be addressed. Email: dwyles{at}ucsd.edu.

	Abstract

Chronic hepatitis C virus infection is a significant worldwide health problem with limited therapeutic options. A number of novel, small molecular inhibitors of HCV replication are now entering early clinical trials in humans. Resistance to small molecular inhibitors is likely to be a significant hurdle to their use in patients. A systematic assessment of combinations of interferon and/or novel anti-hepatitis C virus agents from several different mechanistic classes was performed in vitro. Combinations of inhibitors with different mechanisms of action consistently demonstrated more synergy in combination than did compounds with similar mechanisms of action. These results suggest that combinations of inhibitors with different mechanisms of action should be prioritized for assessment in clinical trials for chronic hepatitis C virus infection.

This article has been cited by other articles:

• Wyles, D. L., Kaihara, K. A., Schooley, R. T. (2008). Synergy of a Hepatitis C Virus (HCV) NS4A Antagonist in Combination with HCV Protease and Polymerase Inhibitors. Antimicrob. Agents Chemother. 52: 1862-1864 [Abstract] [Full Text]