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Article History

Received: 7 March 2025

Revised: 29 May 2025

Accepted: 30 May 2025

First Online: 8 August 2025

Declarations

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: All procedures involving animals were performed following the ARRIVE 2.0 guidelines (Animal Research: Reporting of In Vivo Experiments) and the “European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes” (Strasbourg, 18.III.1986). The use of the frogs was in accordance with the license number LA1210239 to Toxicology and Pharmacology, KU Leuven, and was approved by the Ethical Committee for animal experiments of KU Leuven (P186/2019). Maximum efforts were made to minimize animal suffering and the number of animals used in the experiments.

: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

: Since the discovery of hanatoxin, spider toxins have been widely recognized as voltage sensor modulators of potassium channels. In our research, we identified unique toxins (murinotoxins or MnTx) that inhibit the KV channel pore directly, rather than modulating voltage sensors. Remarkably, these molecules adopt a novel type of fold, distinct from the canonical inhibitor cystine knot (ICK) motif characteristic of spider toxins. The unique pharmacological and structural features of MnTx highlight their significance for both fundamental research and practical applications. These toxins offer exciting potential as innovative tools for probing membrane transport mechanisms and as templates for the development of novel drug candidates.