Protease and helicase activities of hepatitis C virus genotype 4, 5, and 6 NS3-NS4A proteins

Biochemical and Biophysical Research Communications
Marie-Josée MassariolPeter W White

Abstract

The bifunctional NS3 protease-helicase of hepatitis C virus (HCV), together with its cofactor protein NS4A, is an important target for antiviral drugs which can cure HCV infections. HCV strains are divided into six major genotypes based on sequence diversity, and the great majority of reports on NS3 have focused exclusively on genotype 1 proteins. Here we report the cloning, expression, and preliminary characterization of NS3-NS4A gene products from HCV genotypes 4, 5, and 6. This work complements our earlier characterization of genotype 2 and 3 proteins [17]. We compare NS3-NS4A protease and helicase activities of genotypes 4a, 5a, and 6a to those of common reference strains Con1 (genotype 1b) and JFH1 (genotype 2a). The specific activities of the proteases of the newly isolated proteins were similar to those of the reference proteins. Furthermore, the reference inhibitor BILN 2061 had similar activity against all of the proteins except for that of JFH1, which had an apparent K(i) that was 11-fold higher relative to Con1. RNA and DNA unwinding activities were also similar for genotypes 1, 4, 5, and 6 proteins, but significantly higher for genotype 2 JFH1. With the availability of these proteins, inhibitors developed based on t...Continue Reading

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Citations

Dec 29, 2012·The Journal of Biological Chemistry·Jeff A O'MearaMontse Llinàs-Brunet
Oct 26, 2011·Antimicrobial Agents and Chemotherapy·Lisette LagacéGeorge Kukolj
Jan 1, 2016·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Abdo A Elfiky, Wael M Elshemey
May 7, 2020·Journal of Advanced Research·Moustafa E El-ArabyMahmoud A Elfaky
Aug 19, 2010·Journal of Medicinal Chemistry·Montse Llinàs-BrunetPeter W White
Jan 29, 2014·Journal of Medicinal Chemistry·Steven R LaPlanteSteven J Taylor

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