Comparative venomics and preclinical evaluation of antivenoms against Nigeria's "big three" snakes: Naja nigricollis, Bitis arietans, and Echis ocellatus.

Snakebite envenomation is a major yet neglected tropical health burden, causing substantial mortality and morbidity worldwide, particularly in developing regions of sub-Saharan Africa, South Asia, and Southeast Asia. Africa alone is estimated to experience ∼20,000 snakebite deaths annually, although the true burden is likely underestimated because of limited clinical reporting and incomplete hospital-based records. In Nigeria, one of Africa's major snakebite hotspots, most envenomations are attributed to three medically important species: Bitis arietans (puff adder), Echis ocellatus (carpet viper), and Naja nigricollis (black-necked spitting cobra). Despite their overwhelming clinical importance, the composition and biochemical and pharmacological activities of venoms of these species remain poorly characterised, hindering efforts to improve treatment outcomes. This problem is further exacerbated by the limited supply of effective antivenoms, the scarcity of robust preclinical efficacy data, and strong geographic biases in snakebite research. In this study, we comprehensively characterised the venom composition, biochemical properties, pharmacological activities, and toxicity profiles of Nigeria's "big three" medically important snakes. Furthermore, using both in vitro and in vivo approaches, we evaluated the binding and neutralising efficacy of two commercial polyvalent antivenoms, EchiTab-Plus-ICP and PANAF, against these venoms. Our findings fill an important knowledge gap in African snake venom research and provide valuable insights into the effectiveness of currently available antivenoms. These results have important implications for improving the treatment of snakebite envenomation in Nigeria and other parts of sub-Saharan Africa.