Molecular Modeling Approach of Serine Protease NS3-4A Genotype 3a as a Potential Drug Target of Hepatitis C Virus: Homology Modeling and Virtual Screening Study.

Hussain, Rashid; Khalid, Hira; Fatmi, M. Qaiser

Hepatitis C Virus (HCV), affecting millions of people worldwide, is the leading cause of liver disorder, cirrhosis, and hepatocellular carcinoma. HCV is genetically diverse having seven genotypes and several subtypes that are predominant in different regions of the globe. The HCV NS3/4A protease is a major therapeutic target for HCV with various direct acting FDA approved antivirals, and several in clinical development. However, available protease inhibitors (PIs) have lower potency against HCV genotype 3, prevalent in South Asia. Lack of structural data limited our ability to recognize loss of inhibitory potential of PIs. In this study, we attempted to get structural insight of protease GT3 by modeling techniques. The incumbent computational tools were utilized to understand and explore interactions of HCV GT3 receptor with the potential inhibitors after virtual screening of in-house synthesized compound library. The molecular dynamics and pharmacological studies revealed compound Li_PIS_19 exhibiting the favorable binding and better pharmacokinetics properties that may be considered as the most promising compound against HCV GT3 protease. The NS3/4A protease is a major therapeutic target for HCV, responsible for its polyprotein processing. Available protease inhibitors (PIs) have lower potency against NS3 genotype 3 (GT3), prevalent in South Asia. In present study we attempted to get structural insight of protease GT3 by modelling techniques. Incumbent computational tools like molecular docking and molecular dynamics simulations were applied to find suitable PI(s) against NS3 GT3 drug target.

SOUTH Asia; DRUG target; HEPATITIS C virus; UNITED States. Food & Drug Administration; PROTEOLYTIC enzymes; GENOTYPES; MOLECULAR dynamics; MOLECULAR docking

Journal of Computational Biophysics & Chemistry, 2021, Vol 20, Issue 6, p631

2737-4165

Academic Journal

10.1142/S273741652150037X