Hepatitis C virus (HCV), the major cause of non-A/non-B hepatitis and linked to development of heparocellular carcinoma, is a member of the flavivirus family, with a positive-strand RNA genome. This genome encodes a precursor polyprotein that is cleaved co- or posttranslationally into mature viral polypeptides. Part of this cleavage is accomplished via the virally-encoded protease NS3. We have determined the 2.4-E structure of the NS3 protease (NS3P) as part of a program to design specific inhibitors as therapeutic agents for the treatment of HCV infections. For high resolution structures of HCV NS3P in complex with designed inhibitors the use of synchrotron radiation is essential.
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