Alpha-type phospholipase A2 inhibitors from snake blood

Abstract

It is of popular and scientific knowledge that toxins from snake venom (among them the PLA₂ and myotoxins) are neutralized by various compounds, such as antibodies and proteins purified from animal blood. Venomous and nonvenomous snakes have PLA₂ inhibitory proteins, called PLIs, in their blood serum. One hypothesis that could explain the presence of these PLIs in the serum of venomous snakes would be self-protection against the enzymes of their own venom, which eventually could reach the circulatory system. However, the presence of PLIs in non-venomous snakes suggests that their physiological role might not be restricted to protection against PLA₂ toxins, but could be extended to other functions, as in the innate immune system and local regulation of PLA₂s. The present study aimed to review the currently available literature on PLA₂ and myotoxin alpha inhibitors present in snake plasma, thus helping to improve the research on these molecules. Furthermore, this review includes current information regarding the mechanism of action of these inhibitors in an attempt to better understand their application, and proposes the use of these molecules as new models in snakebite therapy. These molecules may help in the neutralization of different types of phospholipases A₂ and myotoxins, complementing the conventional serum therapy.

Keywords: Myotoxin; Myotoxin inhibitor; Phospholipases A2; Snake blood; αPLI.

Fig. 1

In silico model of αBaltMIP trimer (available at Model Archive database under the DOI 10.5452/ma-a4btt) and αBaltMIP monomer (available at Model Archive database under DOI 10.5452/ma-a2iil) with a detailed view of the central pore (yellow), highlighting the four conserved cationic residues R38, K52, R89 and H90. In addition, the hydrophobic core (cyan), the 13–36 residues of the neck C-terminal region (red) and the Y144 (blue) are depicted