Discovery of Novel Peptidomimetic Template for Hepatitis C Virus (HCV) Genotype 4 Inhibition
Eman M. El labbad
Eman Moussa El-labbad
Department of Pharmaceutical Chemistry
Faculty of pharmacy
Ain Shams University
Cairo, Egypt
Abstract:
Hepatitis C virus (HCV) infection has been declared as global health problem in 2007 and approximately 3% of the world's population (roughly 120-180 million people) is estimated to be infected with HCV. Genetically, there are eleven major genotypes. Genotype 4 is principally found in the Middle East, Egypt, and central Africa. The inadequate efficacy and tolerability of the current therapy which is based on interferon and ribavirin warranted significant efforts towards the development of new HCV therapeutics. The present study involved the design of new peptidomimetic template for HCV genotype 4 NS3 protease inhibitors. The design was supported by molecular modeling docking study using Accelyrs Discovery Studio 2.5 Cdocker protocol. The designed molecules that have high docking scores and optimum field alignments were synthesized and biologically evaluated for their in vitro anti-HCV genotype-4 activity. The in vitro study measured the effect of the tested designed molecules on the viral load of standardized cell culture system of HepG2 cell line inoculated with HCV genotype 4 extracted from infected patient serum. Most of the tested compounds showed 50-90% inhibition of Hepatitis C viral load, at micro-mole dose level, against untreated HCV positive control using RT-PCR.
