Abstract
The global re-emergence of the Monkeypox Virus (MPXV) has sparked renewed efforts to identify effective antiviral treatments. In this study, we conducted an in silico docking analysis using CB Dock2 to evaluate natural products and repurposed antiviral drugs. We focused on key viral targets for inhibition, including VP39 2'-O Methyltransferase, viral topoisomerase-DNA complexes, and poxin. Our findings highlighted several natural compounds, such as Physalin A, Sitoindoside IX, Withanolide, Shatavarin 1, Kutkoside, and Berberine HCl, as potential inhibitors. Additionally, Tecovirimat emerged as the most effective repurposed antiviral. Among the natural products, Withanolide, Sitoindoside IX, and Physalin A demonstrated promising inhibitory potential based on their Vina scores and binding affinities, offering hope for alternative therapeutic options. Tecovirimat, however, remained the most potent inhibitor across all tested targets, underscoring its continued relevance in the fight against MPXV.