Dual Modulation of Hemostasis Using Physalia physalis Venom: Insights into Thrombin-Like and Fibrinolytic Activities

Physalia physalis, commonly known as the Portuguese man o’ war, is a venomous cnidarian frequently observed in the Atlantic Ocean. Contact with its tentacles may result in local and systemic symptoms, including interference with the human hemostatic system. Despite increasing clinical reports, the molecular basis of these effects remains poorly understood. In this study, we characterized the enzymatic properties of P. physalis venom obtained through electrostimulation-induced cnidocyte discharge, a method that enables the selective release of venom with minimal structural contamination.

The venom demonstrated a dual modulatory effect on hemostasis. One fraction exhibited potent fibrinolytic and fibrinogenolytic activity, capable of degrading fibrin clots and completely hydrolyzing the α, β, and γ chains of human fibrinogen. The second fraction promoted rapid clot formation through the generation of ~23 kDa fibrin fragments, a hallmark of thrombin-like activity. Enzymatic assays and inhibitor profiling revealed that the fibrinolytic effect was primarily associated with a metalloprotease, whereas the thrombin-like activity was attributed to a serine protease. These enzymes act on different components of the coagulation cascade, suggesting distinct biochemical mechanisms within the same venom source.

The discovery of both fibrinolytic and thrombin-like functions within P. physalis venom represents a novel insight into cnidarian envenomation. It also emphasizes the biochemical diversity of marine venoms and their potential application in therapeutic development. These results not only improve our understanding of venom-induced coagulopathies but also support the exploration of marine-derived enzymes as lead candidates for new anticoagulant or procoagulant drugs.