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Scientific result | Pharmacology | High-throughput screening

Pain: a promising toxin isolated from a spider venom


A collaboration between SIMOPRO, Sanofi R & D, Smartox Laboratories and the Thorax Institute, has isolated a toxin with antinociceptive properties from a high-throughput electrophysiological screening of a collection of more than 100 venoms. Cyriotoxin-1a has been identified, sequenced, chemically synthesized and functionally characterized - from cell to in vivo organism.

Published on 11 March 2019

​Abstract from the original paper:

Background and Purpose

NaV1.7 channel subtype is highly expressed in dorsal root ganglia of the sensory nervous system and plays a central role in the pain signaling 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.

Key Results

We identified cyriotoxin‐1a (CyrTx‐1a), a novel peptide isolated from Cyriopagopus schioedtei spider venom, as a candidate for further characterization. This 33 amino acids toxin belongs to the inhibitor cystine knot structural family and inhibits hNaV1.1‐1.3 and 1.6‐1.7 in the low nanomolar range, compared to the micromolar range for hNaV1.4‐1.5 and 1.8. CyrTx‐1a was 920 times more efficient at inhibiting tetrodotoxin (TTX)‐sensitive than TTX‐resistant sodium currents recorded from adult mouse dorsal root ganglia neurons and in vivo electrophysiological experiments showed that CyrTx‐1a was approximately 170 times less efficient than huwentoxin‐IV at altering mouse skeletal neuromuscular excitability properties. CyrTx‐1a exhibited an analgesic effect in mice by significantly increasing reaction time in the hot‐plate assay.

Conclusions and Implications

The pharmacological profile of CyrTx‐1a paves the way for further engineering studies aimed to optimize the potential antinociceptive properties of this peptide.


Schematic representation of the peptide backbone folding of cyriotoxin-1a determined by NMR. The topology includes an antiparallel beta sheet. The 3 disulfide bridges established between cysteines are colored in yellow. The hydrophobic, basic and acidic residues are respectively colored in green, blue and red. The structure was realized with the PyMol software.

© T.C. Gonçalves et al. 2019 / BJPharm






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