In Silico Analysis of Ergosterol as Antiviral Agents Targeting Monkeypox Methyltransferase, Phosphatase and A42R Profilin-like Protein Receptors

Abstract Phytosterols derived from medicinal mushrooms have emerged as promising therapeutic agents due to their high pharmacological effects, low toxicity, and high bioavailability. The increased concern about virus spread and treatment strategies following the pandemic has necessitated the discovery of new antiviral agents against various concerning viral species. This study investigated the inhibitory effects of ergosterol and its derivative phytosterols on monkeypox target proteins through in silico methods. For comparative analysis, two FDA-approved monkeypox drugs, Tecovirimat and Cidofovir, were used as controls. Key findings revealed that β-ergosterol effectively inhibited the methyltransferase VP39 protein with a binding affinity of −8.9 kcal/mol. Ergosterol peroxide showed the highest affinity for the A42R profilin-like protein, with a binding score of −8.1 kcal/mol, while ergosterol exhibited strong binding with phosphatase, also at −8.1 kcal/mol. These findings indicate that these phytosterols may serve as antiviral agents due to their comparable binding affinities. Compared to the control groups, ergosterol and its derivatives demonstrated significant in silico antiviral activity against monkeypox. Further preclinical studies, including experimental validation, are recommended to confirm these findings and explore their therapeutic potential.