Abstracts of Oral Presentations

• Publisher: Wiley (John Wiley & Sons)
• Year: 2003
• Tongue: English
• Weight: 243 KB
• Volume: 71
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.10454

✦ Synopsis

Hepatitis C virus (HCV) infection is the leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It has been estimated that 3% of the world population is infected with this virus and the current available treatments are of limited efficacy. One of the most intensively studied and best characterized target in the HCV genome is the serine protease of the NS3 protein. This protease is responsible for the maturation of the viral polyprotein precursor and was shown to be essential for replication. Using NMR and computational chemistry methods, we have characterized the interaction between the NS3 protease and various substrate-based peptide inhibitors, and determined their enzyme-bound conformations. This structural information has allowed the design of a novel substituent for the 4-hydroxyproline found at the P2 position of our peptide inhibitors, as well as the design of potent P1 to P3 macrocyclic inhibitors. In addition, these novel inhibitors are highly specific and have the required potency and biopharmaceutical properties to become a new class of antiviral agents for the treatment of HCV infection.