Snake venom phospholipase A2 (North American Pit Viper) (svPLA2)

Snake venom phospholipase A2 (svPLA2) enzymes are a diverse family of proteins found in the venom of North American pit vipers, including rattlesnakes (Crotalus), copperheads, and cottonmouths (Agkistrodon). These enzymes primarily function by hydrolyzing the sn-2 ester bond of glycerophospholipids, leading to the destruction of cell membranes and the release of inflammatory mediators like arachidonic acid (PMID: 30103414). In North American pit vipers, a specialized group of svPLA2s, exemplified by the Mojave toxin, acts as potent presynaptic neurotoxins that block acetylcholine release at the neuromuscular junction, resulting in systemic paralysis (PMID: 28438918). These toxins are major drivers of the clinical manifestations of envenomation, including local tissue necrosis, systemic myotoxicity, and coagulopathy. Therapeutic strategies focus on neutralizing these enzymes using polyvalent antivenoms like CroFab and Anavip, which contain antibodies that bind and sequester the toxins (PMID: 25533131). Furthermore, the small-molecule inhibitor varespladib is being developed as a broad-spectrum treatment to rapidly inhibit svPLA2 enzymatic activity following a snakebite (PMID: 27373742).

Other names

Mojave toxinCrotoxin-like PLA2Presynaptic neurotoxic PLA2Phosphatidylcholine 2-acylhydrolasesPLA2 Group IIAsPLA2 Group IIB

Neutralization of enzymatic and non-enzymatic toxic sites via antibody binding or small-molecule competitive inhibition of the catalytic site.