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 Na V 1.6 and Na V 1.7, as well as the cockroach BgNa V 1 channel. Increased currents through Na V 1.6 and BgNa V 1 channels were associated with bigger window currents and inhibition of inactivation. Decreased Na V 1.7 currents were associated with smaller conductance. Crude venom and TCh3 toxin inhibited action potential generation in invertebr...

Engineering a wolf spider A-family toxin towards increased antimicrobial activity but low toxicity

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Engineering a wolf spider A-family toxin towards increased antimicrobial activity but low toxicity

Abstract

Spider-derived peptides with insecticidal, antimicrobial and/or cytolytic activities, also known as spider venom antimicrobial peptides (AMPs), can be found in the venoms of RTA-clade spiders. They show translational potential as therapeutic leads. A set of 52 AMPs has been described in the Chinese wolf spider (Lycosa shansia), and many have been shown to exhibit antibacterial effects. Here we explored the potential to enhance their antimicrobial activity using bioengineering. We generated a panel of artificial derivatives of an A-family peptide and screened their activity against selected microbial pathogens, vertebrate cells and insects. In several cases, we increased the antimicrobial activity of the derivatives while retaining the low cytotoxicity of the parental molecule. Furthermore, we injected the peptides into adult Drosophila suzukii and found no evidence of insecticidal effects, confirming the low levels of toxicity. Our data therefore suggest that spider venom linear peptides naturally defend the venom gland against microbial colonization and can be modified into more potent antimicrobial agents that could help to battle infectious diseases in the future.


Dersch, L., Stahlhut, A., Eichberg, J., Paas, A., Hardes, K., Vilcinskas, A., & Lüddecke, T. (2024). Engineering a wolf spider A-family toxin towards increased antimicrobial activity but low toxicity. Toxicon, 107810. https://doi.org/10.1016/j.toxicon.2024.107810