Phospholipase A2 toxins (from Naja naja, Bungarus caeruleus, Daboia russelli, and Echis carinatus) (svPLA2)

Phospholipase A2 (PLA2) toxins are a primary and highly destructive component of the venom from the Indian 'Big Four' snakes: the Indian Cobra (Naja naja), Common Krait (Bungarus caeruleus), Russell's Viper (Daboia russelli), and Saw-scaled Viper (Echis carinatus). These enzymes function by hydrolyzing the sn-2 ester bond of glycerophospholipids, leading to the release of arachidonic acid and lysophospholipids, which causes extensive cell membrane damage and triggers inflammatory cascades (Lewin et al., 2016, J. Med. Toxicol.). In clinical envenomation, these toxins exhibit diverse pharmacological effects including presynaptic neurotoxicity leading to respiratory failure, systemic myotoxicity causing muscle breakdown, and hemotoxicity that disrupts the coagulation cascade (Gutierrez et al., 2017, Nature Reviews Disease Primers). While traditional treatment relies on polyvalent antivenoms derived from animal sera, these toxins are the focus of modern drug development targeting small-molecule inhibitors. Varespladib and its oral prodrug methylvarespladib have emerged as potent, broad-spectrum inhibitors that can neutralize the enzymatic activity of PLA2s across these diverse species, potentially serving as a bridge-to-hospital treatment (Lewin et al., 2016, CPT Pharmacometrics Syst. Pharmacol.). Understanding the structural nuances between the Group I PLA2s of elapids (Naja, Bungarus) and Group II PLA2s of vipers (Daboia, Echis) is essential for the design of next-generation pan-specific snakebite therapeutics.

Other names

Snake venom phospholipase A2Group I phospholipase A2 (Elapidae)Group II phospholipase A2 (Viperidae)Phosphatidylcholine 2-acylhydrolaseLecithinase A

Neutralization of toxic enzymatic activity via antibody binding (antivenom) or competitive inhibition of the catalytic active site (Varespladib).