The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway

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  The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway Abstract Introduction:  Voltage-gated sodium channel (VGSC) dysregulation, particularly of the Nav1.6 subtype, is a core mechanism underlying epileptogenesis and its associated neuropsychiatric comorbidities. The scorpion venom peptide BmK AS has demonstrated anticonvulsant potential, but its efficacy in chronic epilepsy and the precise mechanisms of action remain undefined. Methods:  Here, we show that BmK AS exerts robust anti-epileptic and neuroprotective effects through converging mechanisms. In a kainic acid-induced mouse model, BmK AS treatment reduced mortality and seizure parameters. Electrophysiological studies assessed BmK AS modulation of VGSC subtypes. The functional relevance of Nav1.6 targeting was confirmed by the loss of BmK AS’s anti-seizure efficacy upon its pharmacological blockade in a PTZ-in...

Pirates of the coagulase: Clinical implications of dramatic ontogenetic shifts in Yellow Beard (Bothrops atrox) lancehead pitviper Factor Va-mediated venom activation of blood clotting factors

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Pirates of the coagulase: Clinical implications of dramatic ontogenetic shifts in Yellow Beard (Bothrops atrox) lancehead pitviper Factor Va-mediated venom activation of blood clotting factors

ABSTRACT

Bothrops atrox (Yellow Beard Lancehead Pitviper) is responsible for the majority of snakebite morbidity in the Amazon, yet the biochemical basis and clinical consequences of its ontogenetic venom variation remain incompletely resolved. We compared Colombian neonate and adult B. atrox venoms across plasma and fibrinogen clotting assays, thromboelastography, antivenom neutralisation, and clotting factor zymogen activation with defined cofactor conditions. Neonate venom clotting was faster on plasma, whereas adult venom showed stronger thrombin-like (pseudo-procoagulant) action on fibrinogen. All three regional antivenoms neutralised both age classes to varying degrees, with Butantan outperforming ICP and Antivipmyn-Tri. For all antivenoms, neutralisation was consistently better for adult venom. Factor-activation assays revealed activation of prothrombin and Factor VII by both age classes, with a stronger neonate signal. Prothrombin activation strictly required Factor Va as an obligate cofactor; neonate venom could generate usable FVa from FV in addition to using endogenous (thrombin-produced) FVa, while adult venom depended on endogenous FVa. Strikingly, we demonstrate Factor VII activation by B. atrox for the first time and show that FVa markedly potentiates this reaction, including FVa produced by venom cleavage of FV, with age-class differences in the efficiency of venom-produced FVa utilisation. Unlike prothrombin, the neonate venom was able to activate FVII in the absence of FVa, but at much lower levels. Metalloproteases being responsible for prothrombin activation was confirmed with the selective inhibitor prinomastat. These data resolve the mechanistic drivers of ontogenetic potency shifts and explain antivenom performance differences, with immediate implications for antivenom formulation and adjunctive inhibitor use.
Jordan, K., Champagne, P. S., Seneci, L., & Fry, B. G. (2026). Pirates of the coagulase: Clinical implications of dramatic ontogenetic shifts in Yellow Beard (Bothrops atrox) lancehead pitviper Factor Va-mediated venom activation of blood clotting factors. Toxicon, 109025. https://doi.org/10.1016/j.toxicon.2026.109025