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The NS3/4A proteinase of the hepatitis C virus: unravelling structure and function of an unusual enzyme and a prime target for antiviral therapy
Author(s) -
Bartenschlager R.
Publication year - 1999
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1046/j.1365-2893.1999.00152.x
Subject(s) - ns3 , virology , hepatitis c virus , serine proteinase inhibitors , serine , ns2 3 protease , enzyme , biology , rna , flaviviridae , hepatitis c , virus , hepacivirus , biochemistry , serine protease , protease , gene
The hepatitis C virus (HCV) is a major causative agent of transfusion‐acquired and sporadic non‐A, non‐B hepatitis worldwide. Infections most often persist and lead, in ≈ 50% of all patients, to chronic liver disease. As is characteristic for a member of the family Flaviviridae , HCV has a plus‐strand RNA genome encoding a polyprotein, which is cleaved co‐ and post‐translationally into at least 10 different products. These cleavages are mediated, among others, by a virally encoded chymotrypsin‐like serine proteinase located in the N‐terminal domain of non‐structural protein 3 (NS3). Activity of this enzyme requires NS4A, a 54‐residue polyprotein cleavage product, to form a stable complex with the NS3 domain. This review will describe the biochemical properties of the NS3/4A proteinase, its X‐ray crystal structure and current attempts towards development of efficient inhibitors.