Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors

Abstract

Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A₂ (SvPLA₂) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA₂ catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom's adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA₂ toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A₂, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA₂, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA₂ effect.

Keywords: Anticoagulation; Cytotoxicity; Inflammation; Myonecrosis; Phospholipase A2; Snake envenomation.