Snake venom phospholipase A2 (svPLA2)

Snake venom phospholipases A2 (svPLA2s) are a diverse family of enzymes found in the venoms of vipers, cobras, and other venomous snakes, where they serve as primary toxic components. They catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids, releasing lysophospholipids and arachidonic acid, which leads to membrane disruption and the production of inflammatory mediators (PubMed: 30894576). Beyond their enzymatic activity, many svPLA2s exhibit non-enzymatic toxicities by binding to specific receptors on neurons and muscle cells, causing irreversible neuromuscular blockade and extensive myonecrosis (WHO: Snakebite Envenoming). Due to their critical role in snakebite-induced morbidity and mortality, svPLA2s are high-priority targets for next-generation therapeutics. Small molecule inhibitors such as varespladib are currently being repurposed as broad-spectrum, field-deployable treatments to bridge the gap between the bite and hospital-based antivenom administration (PubMed: 27381958).

Other names

Ophidian phospholipase A2Secretory phospholipase A2 (Group I and Group II)Phosphatidylcholine 2-acylhydrolasePLA2Lecithinase A

Small molecule inhibitors like varespladib act as competitive inhibitors that bind to the active site of the enzyme, specifically interacting with the catalytic His-Asp dyad and the calcium-binding loop to prevent phospholipid hydrolysis. Therapeutic antibodies in antivenom work through sequestration and neutralization of the toxin, preventing it from reaching or binding to target tissues.