Structure-based design of inhibitors of NS3 serine protease of hepatitis C virus.

Peptide-Based Inhibitors of Hepatitis C Virus NS3 Serine Protease: Kinetic Aspects and Inhibitor Design

The design of a potent inhibitor of the hepatitis C virus NS3 protease: BILN 2061--from the NMR tube to the clinic.

The virally encoded serine protease NS3/NS4A is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. Until very recently, the design of inhibitors for the HCV NS3 protease was limited to large peptidomimetic compounds with poor pharmacokinetic properties, making drug discovery an ...

Identification of Novel Hepatitis C Virus NS3-4A Protease Inhibitors by Virtual Screening Approach

Hepatitis C Virus (HCV) is a leading cause of cirrhosis and liver cancer worldwide. The replication and viral polyprotein maturation of HCV crucially depends on the cleavage of the polyprotein precursor into 10 viral proteins. The NS3-4A serine protease cleaves the nonstructural region of the polyprotein at four out of five junctions, thus is a promising target for the development of antiviral ...

Affinity selection of a camelized V(H) domain antibody inhibitor of hepatitis C virus NS3 protease.

The HCV genome encodes, within the NS3 gene, a serine protease whose activity specifically cleaves the viral polyprotein precursor. Proteolytic processing of HCV polyprotein precursor by the viral NS3 proteinase is essential for virion maturation and designing specific inhibitors of this protease as possible anti-viral agents is a desirable and practical objective. With a view to studying both ...

Genetic screen for monitoring hepatitis C virus NS3 serine protease activity.

We have developed a genetic system to monitor the activity of the hepatitis C virus (HCV) NS3 serine protease. This genetic system is based on the bacteriophage lambda regulatory circuit where the viral repressor cI is specifically cleaved to initiate the switch from lysogeny to lytic infection. An HCV protease-specific target, NS5A-5B, was inserted into the lambda phage cI repressor. The targe...