Secreted phospholipase A2 (snake venom) (svPLA2)

Secreted phospholipase A2 (sPLA2) enzymes are a diverse family of proteins that constitute a major toxic component of snake venoms from the Viperidae and Elapidae families (UniProt, 2024). These enzymes catalyze the calcium-dependent hydrolysis of the sn-2 position of membrane glycerophospholipids, releasing arachidonic acid and lysophospholipids which trigger inflammatory cascades and cause direct cellular damage (PubMed, 2023). The biological effects of snake venom sPLA2s (svPLA2s) are extensive, encompassing neurotoxicity, myotoxicity, cardiotoxicity, and anticoagulant activities, often leading to severe tissue necrosis or paralysis in envenomated victims (WHO, 2021). As a therapeutic target, svPLA2s are of high interest because their enzymatic activity is a key driver of both systemic toxicity and local tissue destruction. Small-molecule inhibitors such as varespladib and its prodrug methyl-varespladib are currently being investigated as broad-spectrum treatments to neutralize these enzymes across various snake species (Lewin et al., 2016). By inhibiting the catalytic site of svPLA2, these drugs aim to halt the progression of venom-induced pathologies before or alongside the administration of traditional antibody-based antivenoms.

Other names

Phosphatidylcholine 2-acylhydrolaseLecithinase ASnake venom sPLA2Group I phospholipase A2Group II phospholipase A2

Competitive inhibition of the sPLA2 enzyme active site, preventing the hydrolysis of phospholipids and the subsequent release of inflammatory mediators and toxins (Lewin et al., 2016, J Trop Med Hyg).