Snakebite knowledge among healthcare workers in Gabon: A health facility-based cross-sectional survey

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  Snakebite knowledge among healthcare workers in Gabon: A health facility-based cross-sectional survey Abstract Background Snakebite envenoming remains a neglected health issue in many countries, including Gabon, where the limited availability of snakebite-specific training, clinical guidelines, and essential resources at health facilities may lead to gaps in healthcare workers’ knowledge and confidence and the use of non-recommended treatment practices. This study aimed to assess healthcare workers’ knowledge of snakebite management in the Ogooué et des Lacs department of Moyen-Ogooué province in Gabon. Methods From June to August 2023, we conducted a cross-sectional survey targeting all healthcare workers in Ogooué et des Lacs who may be involved in snakebite management. We collected information on prior training, self-perceived knowledge of snakebite management, symptom recognition, clinical management practices, and snake identification. Knowledge was assessed using 10 true/fa...

A hydrophobic loop of the spider-venom peptide Tl1a drives activity at NaV1.8

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A hydrophobic loop of the spider-venom peptide Tl1a drives activity at NaV1.8

Abstract

Voltage-gated sodium (NaVs) channels are pore-forming transmembrane proteins that regulate the influx of sodium ions across cell membranes. Spider venoms are a rich source of NaV-modulating peptides with high selectivity and potency, making them important tools for understanding NaV structure and function. NaV1.8 is tetrodotoxin-resistant, expressed in the peripheral nervous system and contributes to the propagation of action potentials in nociceptive neurons, making it a potential therapeutic target for pain. We identified Tl1a, a 36 amino acid residue peptide isolated from the crude venom of the Peruvian tarantula species, Thrixopelma longicolli, as a modulator of NaV1.8. Tl1a was synthesized using solid-phase peptide synthesis, and activity was assessed using automated whole-cell patch-clamp recordings. Tl1a inhibited NaV1.8 peak current (IC50 210 nM), delayed the kinetics of activation, inhibited fast inactivation, and caused a persistent current as well as a depolarising shift in the voltage dependence of activation (ΔV1/2 +11 mV). Tl1a inhibited peak current with similar potency at NaV1.5 (IC50 282 nM) and KV2.1 (IC50 156 nM) and was 8-fold selective over the tetrodotoxin-sensitive NaV1.4 (IC50 1769 nM), NaV1.1 (2201 nM) and 6-fold selective over NaV1.7 (IC50 1278 nM) channels. Tl1a analogues with an increased number of charged amino acids in loop 4 of the peptide lost activity at NaV1.8 due to altered interactions with the domain IV S3-S4 extracellular loop. The results of this work contribute to a better understanding of the structure-activity relationships at tetrodotoxin-resistant NaV channels and may be useful for the future rational design of selective NaV1.8 peptide modulators.
Thapa, A., Tran, H., Ragnarsson, L., Keramidas, A., Herzig, V., Brinkwirth, N., Deuis, J. R., & Vetter, I. (2025). A hydrophobic loop of the spider-venom peptide Tl1a drives activity at NaV1.8. European Journal of Pharmacology, 177751. https://doi.org/10.1016/j.ejphar.2025.177751