Despite being famous as 'the king' of the snake world, the king cobra (Ophiophagus hannah) has remained a mysterious species, particularly with respect to its venom ecology. In contrast, venom research has largely focussed on the 'big four' snakes that are greatly responsible for the burden of snakebite in the Indian subcontinent. This study aims to bridge the current void in our understanding of the O. hannah venom by investigating its proteomic, biochemical, pharmacological, and toxinological profiles via interdisciplinary approaches. Considering their physical resemblance, the king cobra is often compared to the spectacled cobra (Naja naja). Comparative venomics of O. hannah and N. naja in this study provided interesting insights into their venom compositions, activities, and potencies. Our findings suggest that the O. hannah venom, despite being relatively less complex than the N. naja venom, is equally potent. Finally, our in vitro and in vivo assays revealed that both Indian polyvalent and Thai Red Cross monovalent antivenoms completely fail to neutralise the O. hannah venom. Our findings provide guidelines for the management of bites from this clinically important yet neglected snake species in India.
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