The potential inhibitory mechanism of EGCG against the Chikungunya virus targeting non-structural protein 2 through molecular dynamics simulation

Abstract

This study explores the potential of Indonesian herbal compounds against the chikungunya virus (CHIKV), which causes widespread illness without a specific cure known as chikungunya fever (CHIKF). By focusing on the nsP2 protein, crucial for the virus’s replication, the research utilizes computational methods identifying inhibitor compounds with high binding affinity. These promising candidates are further analyzed through 1 µs of molecular dynamic (MD) simulation studies, aiming to find effective inhibitors to control the chikungunya spread, leveraging Indonesia’s rich biodiversity for novel anti-CHIKV therapies. The results of our study highlight the molecular mechanism of the potential of epigallocatechin 3-O-gallate (EGCG) from Camelia sinensis in inhibiting nsP2 protease by binding to essential catalytic residues and exploring more energetically favorable orientations within the catalytic pocket. This dynamic binding process suggests that EGCG may disrupt the protease’s catalytic functions, potentially altering domain interactions without compromising the protein’s overall structure. Given nsP2’s minimal homology with human proteins, the risk of cross-reactivity is reduced, making it a suitable target for CHIKV therapy. This study suggests EGCG as a prime candidate for further development as a broad-spectrum inhibitor against CHIKF.