Glycine-rich conotoxins from the Virgiconus clade

•A conotoxin, vi6a, was purified from the venom of C. virgo.•vi6a exhibited inhibitory activity in the calcium imaging of dissociated mouse lumbar DRG neurons.•Intracranial and intraperitoneal injection of vi6a resulted in hyperactivity in mice.•Related conotoxins were identified from other members of the Virgiconus clade.

Cone snails in the Virgiconus clade prey on marine worms. Here, we identify six related conotoxins in the O1-superfamily from three species in this clade, Conus virgo, Conus terebra and Conus kintoki. One of these peptides, vi6a, was directly purified from the venom of C. virgo by following its activity using calcium imaging of dissociated mouse dorsal root ganglion (DRG) neurons. The purified peptide was biochemically characterized, synthesized and tested for activity in mice. Hyperactivity was observed upon both intraperitoneal and intracranial injection of the peptide. The effect of the synthetic peptide on DRG neurons was identical to that of the native peptide. Using the vi6a sequence, five other homologs were identified. These peptides define a glycine-rich subgroup of the O1-superfamily from the Virgiconus clade, with biological activity in mice.