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...

Cross-species snakebite antivenom

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Cross-species snakebite antivenom

Venomous snakebites are a major global health problem, exacerbated by limited excess to effective antivenom treatment. Snake venoms are complex mixtures of toxins that vary widely across snakes and regions. As a result, available antivenoms derived from the plasma of immunized horses or sheep are often effective only against a single species. Moreover, although they can save lives, current antivenom treatments do not prevent tissue damage. In work published in Nature, Ahmadi et al. set out to overcome these limitations by developing a broadly acting antivenom targeting the venom of elapid snakes from sub-Saharan Africa.

The authors first immunized an alpaca and a llama with the venoms of 18 snake species and generated a phage-display library to identify nanobodies, the smallest functional fragments of antibodies, with high affinity and broad neutralization against the most medically relevant toxin families: three-finger toxins, phospholipase A2 and Kunitz-type serine protease inhibitors. Eight of the top nanobodies were then combined into a recombinant antivenom. Pre-incubation experiments in mice, in which venom and the recombinant antivenom are pre-incubated before administration, showed that the antivenom cocktail protected mice from death for 17 out of 18 venoms tested. In a rescue setting, which more closely mimics a real snakebite scenario, the recombinant antivenom performed better than a commercial antivenom and effectively reduced the size of venom-induced skin lesions.

Future work should address technical limitations such as the short half-life of nanobodies in circulation. Although additional commercial hurdles remain in bringing new antivenoms to market, this approach makes strides toward realizing the goal of broadly acting cocktails of antivenom tailored to specific regions.

Marchal, I. Cross-species snakebite antivenom. Nat Biotechnol 43, 1930 (2025). https://doi.org/10.1038/s41587-025-02952-x