An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus

  • Nature. 2003 Nov 13;426(6963):186-9. doi: 10.1038/nature02099.
Daniel Lamarre  1 ,  Paul C Anderson ,  Murray Bailey ,  Pierre Beaulieu ,  Gordon Bolger ,  Pierre Bonneau ,  Michael Bös ,  Dale R Cameron ,  Mireille Cartier ,  Michael G Cordingley ,  Anne-Marie Faucher ,  Nathalie Goudreau ,  Stephen H Kawai ,  George Kukolj ,  Lisette Lagacé ,  Steven R LaPlante ,  Hans Narjes ,  Marc-André Poupart ,  Jean Rancourt ,  Roel E Sentjens ,  Roger St George ,  Bruno Simoneau ,  Gerhard Steinmann ,  Diane Thibeault ,  Youla S Tsantrizos ,  Steven M Weldon ,  Chan-Loi Yong ,  Montse Llinàs-Brunet
Affiliations
  • 1. Department of Biological Sciences Boehringer Ingelheim (Canada) Ltd, Laval, Québec, H7S 2G5, Canada. [email protected]
PMID: 14578911 DOI: 10.1038/nature02099
Abstract

Hepatitis C virus (HCV) Infection is a serious cause of chronic Liver Disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 Protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 Protease Inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 Protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.

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