In silico targeting of pox virus proteins to repurpose triterpenes against monkeypox infection

The multi-county outbreak of monkeypox caused by the monkeypox virus (MPXV) has raised serious health concerns around the globe. WHO has declared it a public health emergency of international concern. Unfortunately, no specific vaccine for MPXV is available to the general population. Hence, repurposing of phytochemicals could aid in developing cost-effective anti-MPXV drugs in a comparatively short period. Triterpenes are natural compounds having numerous therapeutic potentials. However, their inhibitory potential against the MPXV is yet to be investigated. Hence, the present in silico study was aimed to analyze the inhibitory potential of six triterpenes against A26, D13, and H3 proteins of the vaccinia virus that shows a close relationship with MPXV. Results indicated that among six tested triterpenes, madecassic acid and maslinic acid interacted with viral proteins with optimum free energy and best binding efficiency. The formation of H-bonds and non-covalent interactions strengthened the binding of these triterpenes with the pockets of target proteins. Hydrophobic interactions like van der Waals and alkyl/pi-alkyl contacts further stabilized the topology of the protein/ligand complex. Hence, in view of these results, madecassic acid and maslinic acid could be considered potential multi-target drug candidates to develop a cost-effective anti-MPXV therapeutic agent.