From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei

Tânia C. Gonçalves (1, 2, 3) , Evelyne Benoit (2, 4, 3) , Michael Kurz (1) , Laetitia Lucarain (1) , Sophie Fouconnier (1) , Stéphanie Combemale (5) , Lucie Jaquillard (5) , Brigitte Schombert (1) , Jean‐Marie Chambard (1) , Rachid Boukaiba (6) , Gerhard Hessler (7) , Andrees Bohme (1) , Laurent Bialy (7) , Stéphane Hourcade (8) , Rémy Béroud (5, 1) , Michel de Waard (9, 10) , Denis Servent (2, 1, 3) , Michel Partiseti (1)

1 Sanofi R & D, Integrated Drug Discovery, In Vitro Biology & Pharmacology
2 SIMoS - Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO)
3 MTS - Médicaments et Technologies pour la Santé
4 NeuroPSI - Institut des Neurosciences Paris-Saclay
5 Bâtiment Biopolis - Smartox Biotechnology [Saint Martin d'Hères]
6 Sanofi R & D, Integrated Drug Discovery, In Vitro Biology & Pharmacology
7 Sanofi-Aventis Deutschland GmbH
8 Neuroscience Therapeutic Area
9 INSERM U836, équipe 3, Canaux calciques, fonctions et pathologies
10 ITX - ITX - unité de recherche de l'institut du thorax

The Na$_V$ 1.7 channel is highly expressed in dorsal root ganglia of the sensory nervous system and plays a central role in the pain signalling process. We investigated a library prepared from original venoms of 117 different animals to identify new selective inhibitors of this target. EXPERIMENTAL APPROACH : We used high throughput screening of a large venom collection using automated patch-clamp experiments on human voltage-gated sodium channel subtypes and then in vitro and in vivo electrophysiological experiments to characterize the active peptides that have been purified, sequenced, and chemically synthesized. Analgesic effects were evaluated in vivo in mice models. The pharmacological profile of CyrTx-1a paves the way for further molecular engineering aimed to optimize the potential antinociceptive properties of this peptide.

Domaines: Sciences du Vivant [q-bio]; Neurosciences [q-bio.NC]; Sciences pharmaceutiques; Pharmacologie

Tânia C. Gonçalves, Evelyne Benoit, Michael Kurz, Laetitia Lucarain, Sophie Fouconnier, et al.. From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei. British Journal of Pharmacology, 2019, 176 (9), pp.1298-1314. ⟨10.1111/bph.14628⟩. ⟨cea-02121632⟩