Targeting Mpox virus proteins with tea phytochemicals: A computational study

Abstract

The recent Mpox outbreak has highlighted the need for effective antiviral treatments. This study explores the potential of Camellia sinensis phytochemicals as inhibitors of the Mpox virus methyltransferase VP39 using in-silico molecular docking. Twenty-six phytochemicals were docked against the VP39 crystal structure (PDB ID: 8B07) and compared to the native ligand Sinefungin. Myricetin-3-glucoside emerged as the most promising compound with a binding affinity of − 8.5 kcal/mol, forming an extensive hydrogen bonding network and hydrophobic interactions. Structure-activity relationship analysis revealed the importance of hydroxylation patterns and glycosylation in flavonoid binding. Chlorogenic acid (-8.1 kcal/mol) was the top-performing phenolic acid, suggesting the quinic acid moiety's role in complex stabilization. Alkaloids demonstrated weaker binding, while anthocyanins, particularly Petunidin (-8.0 kcal/mol), showed promising results. Key residues involved in ligand binding were identified, including VAL-116, ARG-140, ASP-138, PHE-115, and VAL-139. Drug-likeness and ADME analysis revealed that while some potent binders violated Lipinski's rules, several compounds, including Myricetin, Chlorogenic acid, and Petunidin, combined strong binding with favorable drug-like properties. These findings provide a foundation for the development of Camellia sinensis-derived antiviral agents against Mpox, pending experimental validation.