Snakebite remains the most neglected tropical disease globally, with India experiencing the highest rates of mortality and morbidity. While most envenomation cases in India are attributed to the ‘big four’ snakes, research has predominantly focused on Russell’s viper (Daboia russelii), spectacled cobra (Naja naja), and common krait (Bungarus caeruleus), leading to a considerable gap in our understanding of saw-scaled viper (Echis carinatus carinatus) venoms. For instance, the venom gland transcriptome and inter- and intra-population venom variation in E. c. carinatus have largely remained uninvestigated. A single study to date has assessed the effectiveness of commercial antivenoms against this species under in vivo conditions. To address these crucial knowledge gaps, we conducted a detailed investigation of E. c. carinatus venom and reported the first venom gland transcriptome. A proteotranscriptomic evaluation revealed snake venom metalloproteinases, C-type lectins, L-amino acid oxidases, phospholipase A₂s, and snake venom serine proteases as the major toxins. Moreover, we assessed the intra-population venom variation in this species using an array of biochemical analyses. Finally, we determined the venom toxicity and the neutralising efficacy of a commercial antivenom using a murine model of snake envenoming. Our results provide a thorough molecular and functional profile of E. c. carinatus venom.

Snakebite envenoming causes more than 100,000 deaths annually, with India bearing nearly half of this burden. Current equine plasma–derived antivenoms suffer from variable efficacy, safety concerns, and limited cross-neutralization of geographically diverse venoms. Here, we report a rationally designed recombinant antivenom composed of five nanobodies (V _H Hs) that target the α-neurotoxins, cytotoxins, and phospholipases A ₂ prevalent in the venoms of cobra and king cobra species from India. These V _H Hs were previously identified and functionally validated against homologous toxin families from African elapids. In murine preincubation and rescue models of snakebite envenoming, the cocktail prevented mortality after injection with venom from the monocled cobra ( Naja kaouthia ), both king cobra species ( Ophiophagus kaalinga and Ophiophagus hannah ) from the Western Ghats and Northeast India, and pan-Indian populations of spectacled cobra ( Naja naja ). These findings demonstrate the feasibility of developing broad-spectrum nanobody-based recombinant antivenoms with continent-wide coverage as a safe and regionally adaptable biologic for snakebite envenoming therapy.