High-Throughput Insilico Drug Screen against Mpox Targeted Proteins in Comparison with Repurposed Antiviral Drugs against Natural Compounds

Abstract

The recent resurgence of the Monkeypox Virus (MPXV) has prompted increased efforts to discover effective antiviral treatments. This study utilized an in silico docking approach with CB Dock2 to assess both natural compounds and repurposed antiviral medications. We concentrated on several critical viral targets for inhibition, specifically VP39 2'-O Methyltransferase, viral topoisomerase-DNA complexes, and poxin. Our results identified a number of natural substances, including Physalin A, Sitoindoside IX, Withanolide, Shatavarin 1, Kutkoside, and Berberine HCl, as promising inhibitors. Tecovirimat was found to be the most effective among the repurposed antivirals. Notably, natural products like Withanolide, Sitoindoside IX, and Physalin A showed significant inhibitory potential based on their Vina scores and binding affinities, suggesting they may serve as alternative therapeutic options. Tecovirimat consistently proved to be the most powerful inhibitor among repurposed antivirals across all examined targets, reinforcing its importance in combating MPXV.