A review and in silico screening of plant-derived snake venom/toxin inhibitors: ADMET, druglikeness, and medicinal chemistry profiling

Abstract

Snakebite envenomation remains a pressing global health issue, contributing to high rates of illness and death. It also imposes significant socio-economic burdens on affected communities. Recent conservative estimates suggest that approximately 5.4 million snakebite incidents occur annually, leading to nearly 138,000 fatalities. In Africa alone, as many as 500,000 cases are documented each year. This research seeks to explore phytochemicals reported to exhibit in vitro and in vivo inhibitory effects on snake venom and toxin targets. A systematic review was conducted utilizing six electronic databases for literature searches, including Google Scholar, Web of Science, ScienceDirect, Scopus, Springer, and PubMed. This process identified 213 phytocompounds with inhibitory activity against the specified targets. Computational tools such as SwissADME, pkCSM, ADMETlab, ProTox3, Toxtree, and DataWarrior were employed to assess the absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, alongside other medicinal chemistry properties of these compounds. The results indicate that several plant-derived molecules effectively inhibit snake venom/toxin targets in vitro and in vivo; however, only a few appear suitable for drug development without further modifications. Among the analyzed compounds, the terpenes labdane lactone and labdane trialdehyde, along with the benzenoid anisic acid, exhibited strong antivenom potential. Notably, anisic acid achieved complete (100%) neutralization of lethality and defibrinogenation induced by the venoms of Naja kaouthia, Daboia russelii, Ophiophagus hannah, and Echis carinatus in both in vivo and in vitro studies. Labdane lactone and labdane trialdehyde, which were isolated from Curcuma antinaia and Curcuma zedoaroides, respectively, demonstrated significant venom-inhibitory activity at a concentration of 22.7 μM and 21.9 μM against Ophiophagus hannah venom. Specifically, labdane lactone exhibited an inhibition rate of 83%, while labdane trialdehyde achieved a 62% inhibition rate against the venom of Ophiophagus hannah along with favorable in silico drug-likeness and ADMET profiles.