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Hepatitis C Virus Serine Protease Inhibitors: Current Progress and Future Challenges

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Abstract:

Hepatitis C is a predominantly chronic viral infection, affecting 1-3percent of the world population. The causative agent, the hepatitis C virus (HCV), has a positive strand-RNA genome that is utilized, in infected cells, as an mRNA to drive the synthesis of a large polyprotein precursor. This precursor subsequently undergoes proteolytic maturation to generate all of the functional, both structural and nonstructural proteins necessary for viral replication and assembly. The proteolytic activity that is responsible for the generation of the mature viral polymerase as well as for most of the cleavages occurring in the nonstructural region of the polyprotein is expressed by the virus itself and is contained in its nonstructural protein 3 (NS3). Here, the N-terminal 180 amino acids form a chymotrypsin-like serine protease domain. Full activation of this protease is achieved only after complexation with another viral protein, the cofactor protein NS4A. Together, NS3 and NS4A form the active, heterodimeric serine protease that presently is the target of medicinal chemistry efforts aiming at the development of inhibitors with potential antiviral activity. We here review the recent progress in our understanding of the structure and function of the enzyme and in the development of selective and potent NS3 protease inhibitors.

Keywords: Heptitis C Virus Serine protease Inhibition; NS3; NS3 PROTEASE INHIBITORSNS3 PROTEASE INHIBITORS; POLYPROTEIN PROCESSING; Serine-trap Inhibition; nonstructural Protein 3 (NS3)

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867013372814

Publication date: July 1, 2001

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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