Discovery of Natural-pan Inhibitors by Targeting Snake Venom Secretory Phospholipase A2 through Computational Approaches

Abstract

Phytochemicals have been widely used in pharmaceuticals in recent decades due to their anti-inflammatory, cancer-preventative and cardiovascular-protective properties. These phytochemicals were tested on Crotalus durissus terrificus secretory phospholipase A2 (sPLA2), a significant protein in the release of arachidonic acid from phospholipid membranes, in this study. Circular dichroism showed that the secondary structure of the protein has been altered by treatment with phytochemicals. Another interesting finding was that, although phytochemicals reduced the enzyme activity and part of the drug-induced platelet-aggregation and myotoxicity of sPLA2 by 40 percent on average, they could do nothing to lessen the inflammatory or neurotoxic effects of this substance. These findings support the hypothesis that the protein has two separate pharmacological sites, one associated with the enzyme's active site and the other different from it. We used molecular docking to better understand how phytochemicals and sPLA2 might interact. Our docking findings indicated that additional phytochemicals with comparable structures could bind to sPLA2 via hydrogen-bonded, polar, and hydrophobic interactions. Additionally, the stability of the phytochemicals was double-checked using MD Simulation. The proposed study will help to develop better drug candidates with more therapeutic efficacy and least side effects. More research is needed to determine whether phytochemicals can be used to suppress the sPLA2 enzyme.