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The design of a potent inhibitor of the hepatitis C virus NS3 protease: BILN 2061—From the NMR tube to the clinic by Youla S. Tsantrizos is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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## Abstract 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 extremely challenging endeavor. In our quest for the discovery of a small‐molecule lead that could block replication of the hepatitis C virus by binding to the HCV NS3 protease, the critical protein–polypeptide interactions between the virally encoded NS3 serine protease and its polyprotein substrate were investigated. Lead optimization of a substrate‐based hexapeptide, guided by structural data, led to the understanding of the molecular dynamics and electronic effects that modulate the affinity of peptidomimetic ligands for the active site of this enzyme. Macrocyclic β‐strand scaffolds were designed that allowed the discovery of potent, highly selective, and orally bioavailable compounds. These molecules were the first HCV NS3 protease inhibitors reported that inhibit replication

Who reads The design of a potent inhibitor of the hepatitis C virus NS3 protease: BILN 2061—From the NMR tube to the clinic?

Author

Youla S. Tsantrizos

Publisher

Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0006-3525)

Published

2004

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)