Abstract

Snake, scorpion, and spider envenomation remains a significant global health challenge, with Phospholipase A2 (PLA2) and metalloproteinases recognised as key enzymatic mediators of venom toxicity. Inhibition of these enzymes is therefore a crucial strategy in antivenom development. Although synthetic inhibitors such as varespladib, varespladib-methyl, and darapladib have shown promise, their cytotoxicity underscores the need for safer and more effective alternatives. This study explored the bioactive compounds of Talinum paniculatum as potential antivenom agents. Molecular screening revealed that rutin, kaempferol, quercetin, and talinumoside I exhibited strong binding affinities to PLA2 and metalloproteinases, outperforming reference inhibitors including varespladib, varespladib-methyl, darapladib, marimastat, and ilomastat. Subsequent Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) analyses identified quercetin and kaempferol as superior candidates, demonstrating favourable pharmacokinetic and safety profiles. These findings suggest that quercetin and kaempferol may serve as effective inhibitors of PLA2 and metalloproteinases, and thus hold promise as plant-derived antivenom leads. Further in vitro and in vivo investigations are warranted to validate their therapeutic potential.

Keywords: Rutin; Quercetin; Kaempferol; Varespladib; Envenomation; ADMET