Daboxin P, a phospholipase A₂ of Indian Daboia russelii venom, modulates thrombin‐mediated platelet aggregation

Abstract

Daboxin P, reported earlier from the venom of Daboia russellii, disturbs the blood coagulation cascade by targeting factor X and factor Xa. The present study exhibits that Daboxin P also inhibits platelet aggregation induced by various agonists. The thrombin‐induced platelet aggregation was inhibited maximum whereas inhibition of collagen‐induced platelet aggregation was found to be 50% and no inhibition of adenosine diphosphate (ADP) and arachidonic acid‐induced aggregation was observed. Daboxin P dose‐dependently inhibited the thrombin‐induced platelet aggregation with Anti‐Aggregation 50 (AD50) dose of 55.166 nM and also reduced the thrombin‐mediated calcium influx. In‐silico interaction studies suggested that Daboxin P binds to thrombin and blocks its interaction with its receptor on the platelet surface. Quenching of thrombin's emission spectrum by Daboxin P and electrophoretic profiles of pull‐down assay further reveals the binding between Daboxin P and thrombin. Thus, the present study demonstrates that Daboxin P inhibits thrombin‐induced platelet aggregation by binding to thrombin.

Blood Lines: Intraspecific and Interspecific Variations in Anticoagulant Actions of Agkistrodon Viperid Venoms

“…As the taxa that most potently inhibited FXa do not form a monophyletic clade (Figure 4), this suggests that FXa inhibition is a basal trait within this genus that has been amplified on three occasions and therefore an indication of convergence in adaptation. This is consistent with FXa inhibition having been documented in other pit vipers from the Americas, including the Bothriechis, Bothrops, Cerrophidion, Crotalus, and Ophryacus species [21,22,65,66]; Asian pit vipers, including the Deinagkistrodon and Gloydius species [65,67,68]; true vipers, including the Cerastes, Daboia, Pseudocerastes, and Vipera species [65,[69][70][71][72][73]; and elapid snakes including the Naja and Pseudechis species [14,41,74,75]. The toxin types responsible are diverse, including Kunitz peptides, lectin-framework toxins, and phospholipases A 2 .…”