{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T15:32:43Z","timestamp":1759159963928,"version":"3.41.2"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The venom of <jats:italic>Cyriopagopus schmidti<\/jats:italic> spider has been extensively investigated, thereby allowing the identification of numerous new natural peptides. Many of these peptides are active on ion channels and several of them occur from post-translational processing. In order to further identify new entities, we screened this venom against five different human voltage-gated sodium (hNa<jats:sub>v<\/jats:sub>) channels. We illustrate the unusual richness of this venom in targeting this wide variety of hNa<jats:sub>v<\/jats:sub> channels. We confirm the identity of previously discovered peptides active on these ion channels type (huwentoxin (HwTx)-I, HwTx-II and HwTx-IV), indicating the efficacy of the screening process by automated patch-clamp. We also identified a novel analogue of HwTx-IV that differs by the absence of amidation and the presence of an extra C-terminal Gly residue. Interestingly, this analogue is less potent than HwTx-IV itself in blocking hNa<jats:sub>v<\/jats:sub>1.7 in cell lines, but turns out to be significantly more potent in TTX-sensitive dorsal root ganglia neurons. Because of this unexpected finding, this novel analogue turns out to be a more potent analgesic than HwTx-IV itself without presenting most of the Na<jats:sub>v<\/jats:sub>1.6-related toxic effects of HwTx-IV.<\/jats:p>","DOI":"10.3389\/fphar.2025.1566312","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T12:47:56Z","timestamp":1744289276000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The venom of Cyriopagopus schmidti spider contains a natural huwentoxin-IV analogue with unexpected improved analgesic potential"],"prefix":"10.3389","volume":"16","author":[{"given":"Aur\u00e9lie","family":"Antunes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00f4me","family":"Montnach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuldip","family":"Khakh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludivine","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baptiste","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Ribeiro Oliveira-Mendes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Jaquillard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Servent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9my","family":"B\u00e9roud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles J.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyne","family":"Benoit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"De Waard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.bbamem.2017.01.020","article-title":"Spider peptide toxin HwTx-IV engineered to bind to lipid membranes has an increased inhibitory potency at human voltage-gated sodium channel hNaV1.7","volume":"1859","author":"Agwa","year":"2017","journal-title":"Biochim. 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