Computational study unravels inhibitory potential of epicatechin gallate against inflammatory and pyroptosis-associated mediators in COVID-19

Abstract

Coronavirus disease-19 (COVID-19) is the global health emergency caused by SARS-CoV-2. Upon infection, antigenic determinants of the virus trigger massive production of proinflammatory/pyroptosis-associated proteins, resulting in cytokine storm, tissue damage, and multiorgan failure. Therefore, these proinflammatory/pyroptosis-associated mediators are promising therapeutic targets to combat COVID-19. Epicatechin gallate (ECG) is a polyphenol found in green tea. It has antioxidative and anti-inflammatory properties. Hence, in the present study, ECG was selected to explore its binding potential for inflammatory mediators such as interleukins, interferon-γ (IFNγ), and tumor necrosis factor-α (TNF-α), along with their native receptors. In addition, the interacting potential of ECG with pyroptosis-associated proteins, viz. caspases and BAX has also been investigated. Molecular docking analysis has revealed that ECG interacts with interleukins, IFNγ, TNF-α, cytokine receptors, caspase-1/4/11, and BAX with significant binding affinity. Several amino acid residues of these mediators were blocked by ECG through stable hydrogen bonds and hydrophobic contacts. ECG interacted with caspase-11, BAX, and TNF-R1 with better binding affinities. Therefore, the present in silico study indicates that ECG could be a potential drug to subvert cytokine storm and pyroptosis during COVID-19.