Computational Medicinal Chemistry applications to cure Asian-prevalent strain of Hepatitis C Virus

25 April 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Hepatitis C Virus (HCV), affecting millions of people worldwide, is the leading cause of the liver disorder, cirrhosis, and hepatocellular carcinoma. HCV is genetically diverse having eight gen-otypes and several subtypes predominant in different regions of the globe. The HCV NS3/4A protease is a primary therapeutic target for HCV with various FDA-approved antivirals and several clinical developments. However, available protease inhibitors (PIs) have lower potency against HCV genotype 3 (GT3), prevalent in South Asia. In this study, the incumbent computational tools were utilized to understand and explore interactions of the HCV GT3 receptor with the potential inhibitors after the virtual screening of one million compounds retrieved from the ZINC database. The molecular dynamics, pharmacological studies, and experimental studies uncovered the potential PIs as ZINC000224449889, ZINC000224374291, and ZINC000224374456 and derivative of ZINC000224374456 from the ZINC library. The study revealed that these top hit compounds exhibited good binding and better pharmacokinetics properties that might be considered the most promising compound against HCV GT3 protease. Viability test, on primary healthy Human Gingival Fibroblasts (HGFs) and cancerous AGS cell line were also performed to assess their safety profile after administration. In addition, Surface Plasmon Resonance (SPR) was also performed for determination of affinity and kinetics of synthesized compounds with target proteins.

Keywords

Structure-based drug design
virtual screening
Cell Viability
Surface Plasmon Resonance

Supplementary materials

Title
Description
Actions
Title
Computational Medicinal Chemistry applications to cure Asian-prevalent strain of Hepatitis C Virus
Description
Supplementary Materials
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.