Snake venom enzymatic toxins

Snake venom enzymatic toxins are a diverse group of proteins, including phospholipases A2 (PLA2), snake venom metalloproteinases (SVMP), and snake venom serine proteases (SVSP), that drive the pathology of snakebite envenomation [Gutiérrez et al., 2016]. These enzymes act by degrading the extracellular matrix, disrupting the blood coagulation cascade, and damaging cellular membranes [Slagboom et al., 2017]. Hemotoxic components specifically target the circulatory system, leading to systemic hemorrhage and venom-induced consumption coagulopathy [Isbister, 2010]. In addition to systemic effects, these toxins cause significant local tissue destruction and inflammation at the bite site [WHO, 2021]. Historically, these toxins have been targeted by animal-derived antivenoms which use polyclonal antibodies to neutralize venom components [Casewell et al., 2020]. Modern drug discovery is exploring small-molecule inhibitors such as varespladib (targeting PLA2) and marimastat (targeting SVMPs) as potential adjuncts or field-stable alternatives to antivenom [Lewin et al., 2016; Albulescu et al., 2020]. These inhibitors work by binding to the catalytic sites of the enzymes, thereby preventing the cleavage of physiological substrates [Bulfone et al., 2018].

Other names

Hemotoxic and other enzymatic toxins in snake venomsSnake venom enzymesOphidian enzymatic toxinsHemotoxic snake toxinsSnake venom hydrolases

Neutralization of enzymatic activity through competitive inhibition of the catalytic site or antibody-mediated sequestration and clearance [Lewin et al., 2016; Albulescu et al., 2020].