Oligoclonal nanobody-based recombinant antivenom protects mice challenged with venom from cobras and king cobras from...

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_HHs) that target the α-neurotoxins, cytotoxins, and phospholipases A₂ prevalent in the venoms of cobra and king cobra species from India. These V_HHs 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.