Beyond ST-246: Unveiling Potential Inhibitors Targeting VP37 Protein in Silico From Herb and Marine Databases

Abstract

In pursuit of unraveling novel structural inhibitors for treating monkeypox virus, targeting the VP37 protein, which is bioactive in response to ST-246, to discern pharmaceutical molecules specifically tailored to combat monkeypox virus. We employed a semi-flexible molecular docking, molecular dynamic simulation, and ADME screening methodology, which are based on structure, to screen compounds from CMNPD and TCM in silico. These methodologies allowed us to find potential candidates depending on their binding values and interactions with the binding site of main protease. To further evaluate the stability of these interactions, we conducted molecular dynamics simulations and calculated binding energies. Herein, employing methods such as binding energy calculations, comparative analyses, and molecular dynamics simulations for activity computations, the six top hits of the compounds were validated as five kinds of good inhibitors, surpassing its reference compound ST-246, for better in vitro drug candidates against MPXV.