The chromosome-level genome of Mesobuthus martensii provides insights into its evolution and the diversity of venom peptides

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  The chromosome-level genome of Mesobuthus martensii provides insights into its evolution and the diversity of venom peptides Abstract Mesobuthus martensii , the source species of the traditional Chinese medicine “Quanxie”, has long been utilized for its therapeutic properties. Venom peptides are recognized as the major active molecular basis of these pharmacological activities. Despite this, their development as therapeutic agents remains poorly explored. In this study, we performed an integrated multi-omics investigation to systematically explore the venom peptides of Mesobuthus martensii . We generated a chromosome-level genome assembly of Mesobuthus martensii using third-generation sequencing technologies, yielding a genome size of 1.08 Gb with a contig N50 of 46.46 Mb. Integrated genomic and transcriptomic analyses led to the identification of 51 putative novel venom peptide candidates. From the broader venom peptide set, five lysine- and arginine-rich candidates were select...

Electrophysiological Characterization of the Venom and Toxins from the Scorpion Tityus championi Targeting Voltage-Gated Sodium Channels and Molecular Modeling of Tch3, a Toxin with Therapeutic Potential for Pain Relief

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Electrophysiological Characterization of the Venom and Toxins from the Scorpion Tityus championi Targeting Voltage-Gated Sodium Channels and Molecular Modeling of Tch3, a Toxin with Therapeutic Potential for Pain Relief

Abstract

Scorpion neurotoxins are small peptides that target ion channels and offer opportunities for novel therapeutic discovery. This study analyzed the functional effects of the venom and toxins from the Costa Rican endemic scorpion, Tityus championi. Initially, crude venom was tested on different isoforms of voltage-gated sodium channels. Our findings revealed that the venom contains toxins that affect mammalian NaV1.6 and NaV1.7, as well as the cockroach BgNaV1 channel. Increased currents through NaV1.6 and BgNaV1 channels were associated with bigger window currents and inhibition of inactivation. Decreased NaV1.7 currents were associated with smaller conductance. Crude venom and TCh3 toxin inhibited action potential generation in invertebrate neurons expressing NaV1.7-like channels. In these neurons, Tch2 and Tch4 toxins shifted voltage sensitivity to more negative potentials, ultimately widening the window current but decreasing channel availability. Conversely, Tch3 behaved as an inhibitory toxin, closing window currents and decreasing channel availability. Structural modeling showed that Tch3 adopts an αββ fold and binds the S3–S4 loop of Domain II in human NaV1.7. These data show the diverse effects of scorpion venoms on channels and neurons, characterize its principal toxins, and show that Tch3 has therapeutic potential for pain relief.

Akerman-Sánchez, G., Peigneur, S., Carleer, K., Ortiz, N., Navia, F., Fierro, L., Castaño, S., Díaz, C., Tytgat, J., & Brenes, O. (2026). Electrophysiological Characterization of the Venom and Toxins from the Scorpion Tityus championi Targeting Voltage-Gated Sodium Channels and Molecular Modeling of Tch3, a Toxin with Therapeutic Potential for Pain Relief. Biomolecules. https://doi.org/10.3390/biom16040552