From phytomedicine to conventional drug research, to look for new drug molecule against monkey pox virus; a molecular docking, virtual screening and ADME analysis.

Abstract

Globally, traditional and complementary therapies (such as homeopathy, phytotherapy and herbal medications) are becoming increasingly prevalent alongside modern medical care. The therapeutic substances used in homeopathy and other traditional complementary medicine disciplines are derived from these traditional applications. Numerous notable clinical and preclinical studies have shown their impact during COVID-19. This study aims to investigate the potential antiviral effects of medicinal alkaloids against the monkeypox virus in the current scenario. The structures of 47 known phytochemicals of commonly used medicines in CAM were obtained from PubChem in SDF format, minimized, and then docked against the 3D crystal structure of monkeypox virus methyltransferase VP39 (PDB: 8B07). The results were analyzed, and compounds with significant docking scores were further evaluated. The docking results showed that six compounds-Sarsaponin, Luteolin, Quercetin, Apigenin, and Ducimarine-had better docking scores than Tecovirimat, a standard drug used in managing monkeypox. Additionally, most compounds exhibited better docking scores than Cidofovir, another drug used against monkeypox. Interaction analysis revealed that hydrogen bonding, pi-pi T-shaped, and pi-alkyl interactions were responsible for the observed docking scores. Key amino acid residues involved in the interaction between the compounds and monkeypox virus methyltransferase VP39 included GLY 96, LEU 159, PHE 115, VAL 139, VAL 116, GLY 68, ARG 140, ILE 94, ASN 156, and ARG 156. Five phytochemicals-Luteolin, Quercetin, Apigenin, Sarsaponin, and Ducimarine-show strong potential as monkeypox virus methyltransferase inhibitors. Apigenin and Ducimarine are particularly promising due to their favorable profiles, including no PAINS alerts and good drug-like properties. Sarsaponin, while highly permeable, has high lipophilicity, which may limit its use. Luteolin and Quercetin also show potential but require further investigation due to PAINS alerts.