Secretory phospholipase A2 venom toxins (sPLA2 toxins)

Phospholipase A2 (PLA2) toxins are key virulent factors in the venoms of Crotalus durissus (South American rattlesnake) and Bothrops asper (fer-de-lance), responsible for severe clinical outcomes like neurotoxicity and myonecrosis. In Crotalus durissus, the crotoxin complex is the primary toxin, consisting of an enzymatic PLA2 subunit and a chaperone protein, crotapotin, that facilitates its delivery to nerve terminals (Sampaio et al., 2010). Bothrops asper venoms contain both Asp49 PLA2s, which hydrolyze phospholipids, and Lys49 PLA2-like proteins, which cause membrane rupture through non-enzymatic mechanisms (Gutiérrez & Lomonte, 1995). These toxins act by damaging cell membranes, inducing the release of inflammatory mediators, and blocking neuromuscular transmission at the presynaptic level. Clinically, they lead to symptoms ranging from local tissue destruction to systemic respiratory paralysis. Therapeutic strategies focus on neutralizing these toxins using polyvalent antivenoms or small-molecule inhibitors like varespladib, which competitively binds the PLA2 active site (Lewin et al., 2016). Monitoring efficacy often involves measuring serum creatine kinase levels as a proxy for muscle damage (Lomonte et al., 2003). Understanding the diversity of these PLA2 isoforms is crucial for developing broad-spectrum treatments for snakebite envenomation.

Other names

CrotoxinCrotapotinMyotoxin IMyotoxin IIBasp-IIBasp-IIIGroup IIA phospholipase A2Lys49 myotoxinAsp49 phospholipase A2Basic phospholipase A2

Small molecule inhibitors like varespladib act as competitive inhibitors of the PLA2 active site, preventing phospholipid hydrolysis and subsequent membrane damage. Antivenoms utilize polyclonal antibodies to bind and neutralize the toxins, preventing their interaction with target membranes or receptors.