Classical Molecular Dynamics Simulation identifies Catechin gallate as a Promising Antiviral Polyphenol against MPOX palmitoylated surface protein

Abstract

Cumulative global prevalence of the emergent monkeypox (MPX) infection in the non-endemic countries has been professed as a global public health predicament. Lack of effective MPX-specific treatments sets the baseline of designing of the current study. This research work uncovers the effective use of known antiviral polyphenols against MPX viral infection, and recognise their mode of interaction with the target F13 protein, that plays crucial role in formation of enveloped virions. Herein, we have employed state-of-the-art machine learning based AlphaFold2 to predict the three-dimensional structure of F13 followed by molecular docking and all-atoms molecular dynamics simulations to investigate the differential mode of F13-polyphenol interactions. Our extensive computational approach identifies six potent polyphenols Rutin, Epicatechin gallate, Catechingallate, Quercitrin, Isoquecitrin and Hyperoside exhibiting higher binding affinity towards F13, buried inside a positively charged binding groove. Intermolecular contact analysis of the docked and MD simulated complexes divulges three important residues Asp134, Ser137 and Ser321 that are observed to be involved in ligand binding through hydrogen bonds. Our findings suggest that ligand binding induces minor conformational change in F13 to affect the conformation of the binding site. Concomitantly, essential dynamics of the six-MD simulated complexes reveals Catechin gallate, a known antiviral agent as a promising polyphenol targeting F13 protein, dominated with a dense network of hydrophobic contacts. However, assessment of biological activity of polyphenols needs to be confirmed through in vitro and in vivo assay, which may pave the path for development of new novel antiviral drugs.