Phytochemical profiling and in silico evaluation of Mentha pulegium L. compounds againstmonkeypox virus methyltransferase VP39

This study explores the potential of bioactive compounds from Mentha pulegium L. as inhibitors of the monkeypox virus methyltransferase VP39. High-Performance Liquid Chromatography (HPLC) was employed to identify and characterize phenolic compounds in the plant extract. Computational methods were used to predict drug-likeness and toxicity and to evaluate binding interactions through molecular docking and dynamics simulations.

The aim. To investigate the antiviral potential of M. pulegium compounds against monkeypox virus VP39 by evaluating their drug-likeness, toxicity, and interaction stability through computational approaches.

Materials and methods. Various phenolic compounds in M. pulegium were identified using HPLC. Drug-likeness and toxicity were predicted using SwissADME, ProTox 3.0 Tool, and OSIRIS Property Explorer tools. Molecular docking studies assessed the binding affinity of selected compounds with VP39, and molecular dynamics simulations evaluated the stability of these interactions over time.

Results. Luteolin and rosmarinic acid exhibited the highest binding affinities to VP39, with docking scores of −9.3 kcal/mol and −8.7 kcal/mol, respectively, and formed multiple hydrogen bonds with key amino acid residues including Ile94, Gly96, Phe115, Val139, Ala158, Lys186, and Tyr189 for luteolin, and Gly68, Ile94, Asp95, Val112, Phe115, Val141, and Asn156 for rosmarinic acid. Molecular dynamics simulations showed that these compounds interacted with moderately flexible regions of the enzyme (residues 67–79 and 243–246), with the RMSD stabilizing at around 3.91 Å after 5000 ps, enhancing binding stability and suggesting a strong potential for inhibitory activity.

Conclusion. The findings underscore the potential of luteolin and rosmarinic acid from M. pulegium as promising antiviral agents against the monkeypox virus. This research provides a foundation for further exploration and development of novel therapeutic strategies based on these natural compounds.

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