Proteomic exploration of the recently Re-classified forest cobra Naja species and the potential cytotoxic activity in cancer cell lines

The forest cobra (Naja melanoleuca) species represents one of the most widespread medically important elapid snakes across Africa. The immense tissue-damaging effect of cobra venoms is attributed to the cytotoxins (CTX), which predominate in virtually all cobra venoms. In this study a bottom-up venomic approach was followed for deciphering the composition of the N. melanoleuca, N. subfulva, and N. savannula venom proteomes. The results revealed complex venoms that constituted predominantly of proteins belonging to the three-finger toxins (3FTxs) followed by phospholipase A₂ (PLA₂s) and snake venom metalloproteinases (SVMPs). The cytotoxicity and selectivity of the crude venoms and fractions were evaluated against cancer and normal cell lines. The crude N. melanoleuca venom sample demonstrated weak/low cytotoxic activity across the different cell lines as corroborated by SI values of less than 2, thus highlighting its limited application against these cancer cells, while the N. subfulva venom demonstrated its highest cytotoxic activity against the HeLa cancer cell line with a moderate selectivity index of 2.04. It is crucial to emphasize that these findings are still in the preliminary stages, primarily based on in vitro studies, and there remains a significant gap to bridge before any therapeutic applications can be considered. Significance: Biological significance: African forest cobra venom is a rich source of bioactive compounds such as cytotoxins, which cause tissue necrosis and descending paralysis. However, the venom has also been identified as a potential source of therapeutic agents, including anticancer agents. In this study, we evaluate the anticancer effects of the N. melanoleuca, N. subfulva, and N. savannula venoms and their fractions against the selected cell lines. The 3FTxs and PLA₂s, which are the most abundant protein families in the venoms, are predominantly responsible for the cytotoxic effects. In conclusion, this research study highlights the important role of forest cobra venoms as potential resources that researchers can further exploit to investigate the molecules responsible for the anticancer effect and investigate their mechanisms of action.