In silico identification of potential anti-monkeypox virus agents from Hypericum sampsonii

Abstract

Monkeypox (Mpox), an emerging zoonotic infectious disease caused by the monkeypox virus (MPXV), has become an escalating global health threat. A wave of outbreaks began in 2022 and continued through the end of 2024. Currently, no vaccines or FDA-approved specific treatments exist for MPXV, making the discovery of effective antiviral drugs crucial. The A48R protein, a thymidylate kinase (TK), is recognised as a promising target for MPXV drug development due to its distinctive active site structure compared with the human homolog. Hypericum sampsonii Hance, a traditional medicinal herb from the Guttiferae family, has demonstrated various biological activities, including antiviral properties. By leveraging the natural compounds derived from H. sampsonii, this study aimed to identify potential inhibitors of the MPXV-TK protein. Molecular docking and dynamics simulations revealed two compounds, LTS0126561 and LTS0259892, with strong affinity for the TK active site. In silico pharmacokinetic and toxicological assessments indicated that both compounds are suitable candidates for oral drug development. These identified compounds represent a solid foundation for developing antiviral agents against MPXV and other Orthopoxviruses. However, further experimental validation of these lead compounds is required to confirm their predicted antiviral activities.