Unveiling the Molecular Dialogue between Monkeypox E8 Protein and Punicalagin: Pioneering the New Era of Natural Drugs

Monkeypox has recently surfaced as a public health issue, and the virus has spread rapidly worldwide in the post-COVID-19 period. These emerging infections hinder human health and the advancement of the global economy. There are currently no authorized medications to treat this condition. As a result, this study gap motivates us to seek a viable inhibitor from a natural source. In the present study, 10 plant-derived compounds and commercialized drugs respectively were subjected to molecular docking and 100 ns molecular dynamics simulations to identify the potent inhibitor against MPXV E8 ectodomain protein. Punicalagin showed a greater affinity for the target protein (-9.1 kcal/mol), and maraviroc, among commercial drugs, had a binding affinity of -7.4 kcal/mol which was lower than punicalagin. MD simulations substantiated this study and showed better stability of punicalagin with the target envelope protein, compared to the control drug maraviroc. This finding was validated by decreased RMSD, RMSF, Rg, and SASA values with increased H-bonding. Therefore, we could speculate that the plant-derived natural compound, punicalagin can act as a potent therapeutic against the MPXV.