Hepatitis C virus NS3/4A protease

Despite an urgent medical need, a broadly effective anti-viral therapy for the treatment of infections with hepatitis C viruses (HCVs) has yet to be d eveloped. One of the approaches to anti-HCV drug discovery is the design an d development of specific small molecule drugs to inhibit the proteolytic p rocessing of the HCV polyprotein. This proteolytic processing is catalyzed by a chymotrypsin-like serine protease which is located in the N-terminal r egion of non-structural protein 3 (NS3). This protease domain forms a tight , non-covalent complex with NS4A, a 54 amino acid activator of NS3 protease . The C-terminal two-thirds of the NS3 protein contain a helicase and a nuc leic acid-stimulated nucleoside triphosphatase (NTPase) activities which ar e probably involved in viral replication. This review will focus on the str ucture and function of the serine protease activity of NS3/4A and the devel opment of inhibitors of this activity. (C) 1998 Published by Elsevier Scien ce B.V. All rights reserved.