Predicted Mechanism of Action of Venom Toxins On Testicular Toxicity: An In-Silico Approach

Abstract

Snake envenomation is considered as a neglected disease from world health organization. Recent survey states Indiahas the highest rate of around 1.2 million deaths. As a pathophysiological effect, snake bite is contributing for major toxicity onhuman organ systems. As a secondary outcome of snake bite, testicular toxicity on the later stages of envenomation gaining moreinterest in recent years. But till date none of the studies have explored the field with the major toxins of the viper venom. Basedon the review, our aim of the study was to predict the possible mechanism of action of the viper toxins against testicular toxicity.Hence to achieve the aim of the study, the objectives framed to perform the in-silico docking of major viper venom toxins namelyVRV-PL-V and VRV-PL-VIIIa against human testicular tight junction and extra cellular matrix proteins. Docking results of our datademonstrated the prominent interaction of VRV-Pl-VIIIa with claudin, occludin, TGF-β and Tubulin α/β with the strong hydrogenbonds where as VRV-PL-V exhibited very poor hydrophobic interactions. VRV-PL-V structure was available and hence thestructure was predicted and its stability was confirmed before docking. Occludin, TGF-β and Tubulin-α proteins shared multiplehydrogen bonds with the toxin VRV-PL-VIIIa whereas claudin and Tubulin-α had numerous hydrophobic interactions with theVRV-PL-VIIIa toxin. On discussion, our docking studies state the impressive binding intensity of VRV-PL-VIIIa over VRV-PL-Vwhere it showed binding ability only with Tubulin α and β that too with weak interactions. In conclusion, our overall studies justifythe previous reports of VRV-PL-VIIIa on testicular toxicity.