Harnessing Indian Medicinal Phytochemicals Against Monkeypox Virus Thymidine Kinase: A Virtual Screening and Molecular Dynamics Simulation Study

ABSTRACT

The global re‐emergence of the monkeypox virus (MPXV), a zoonotic orthopoxvirus closely related to variola virus (the causative agent of smallpox), highlights the urgent need for effective antiviral agents, particularly in light of the limited availability for virus‐specific therapeutics. Thymidine kinase (TK), a key enzyme involved in viral DNA replication and nucleotide salvage, represents a promising molecular target for anti‐MPXV drug development. In this study, the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) database was utilized to screen diverse natural phytochemicals with potential TK inhibitory activity. A hierarchical virtual screening workflow comprising high‐throughput (HTVS), standard precision (SP), and extra precision (XP) docking was employed to identify lead compounds with strong binding affinities. The top‐ranked hits exhibited stable conformations, favorable docking scores, and key hydrogen‐bonding interactions within the TK active site. This integrative computational approach provides a foundation for future in vitro and in vivo validation, supporting the discovery of plant‐based inhibitors against MPXV and advancing antiviral drug development for emerging orthopoxviruses.