Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins

Abstract

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.

Exploring the molecular mechanism of Gan Shuang granules for the treatment of non-alcoholic steatohepatitis using network pharmacology, molecular docking, and experimental verification

“…The high-quality 3D structures of small molecules and proteins were exhibited by LIGPLOT + (version v2.2) software. This helped us to clearly observe the type of bonding between the ligands and protein ( Shahid et al, 2021 ).…”

Alkaloids as potential antivirals. A comprehensive review

“…HCV affects about 3% of the world's populace and is the leading cause of chronic liver disease. HCV causes both acute and chronic hepatitis, with symptoms ranging from a brief illness to a serious, life-threatening condition [73,74]. Alkaloids isolated from Z. nitidum (Roxb.)…”

The potential of epigallocatechin gallate in the chemoprevention and therapy of hepatocellular carcinoma

“…Ample evidence has confirmed the potential mechanism by which EGCG retards HCV infection is that EGCG directly changes the viral particle structure of HCV, ultimately reducing the ability of HCV to adhere to the hepatocyte surface ( Ciesek et al, 2011 ; Calland et al, 2012 ; Calland et al, 2015 ). HCV envelope proteins or capsid proteins may be involved in this process ( Mathew et al, 2014 ; Shahid et al, 2021 ). Different from its direct effect on virus particles, EGCG may also inhibit CD81 receptors that is a critical pathway for HCV to enter hepatocytes through upregulating the expression of certain miRNAs, such as miR-548m and miR-194, thus reducing HCV infectivity in Huh7 cell lines ( Mekky et al, 2015 ; Mekky et al, 2019 ).…”