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Publication Abstract from PubMed

Cone snails are a diverse group of predatory marine invertebrates that deploy remarkably complex venoms to rapidly paralyse worm, mollusc or fish prey. omega-Conotoxins are neurotoxic peptides from cone snail venoms that inhibit Cav2.2 voltage-gated calcium channel, demonstrating potential for pain management via intrathecal (IT) administration. Here, we isolated and characterized two novel omega-conotoxins, MoVIA and MoVIB from Conus moncuri, the first to be identified in vermivorous (worm-hunting) cone snails. MoVIA and MoVIB potently inhibited human Cav2.2 in fluorimetric assays and rat Cav2.2 in patch clamp studies, and both potently displaced radiolabeled omega-conotoxin GVIA ((125)I-GVIA) from human SH-SY5Y cells and fish brain membranes (IC50 2-9 pM). Intriguingly, an arginine at position 13 in MoVIA and MoVIB replaced the functionally critical tyrosine found in piscivorous omega-conotoxins. To investigate its role, we synthesized MoVIB-[R13Y] and MVIIA-[Y13R]. Interestingly, MVIIA-[Y13R] completely lost Cav2.2 activity and MoVIB-[R13Y] had reduced activity, indicating that Arg at position 13 was preferred in these vermivorous omega-conotoxins whereas tyrosine 13 is preferred in piscivorous omega-conotoxins. MoVIB reversed pain behavior in a rat neuropathic pain model, confirming that vermivorous cone snails are a new source of analgesic omega-conotoxins. Given vermivorous cone snails are ancestral to piscivorous species, our findings support the repurposing of defensive venom peptides in the evolution of piscivorous Conidae.

Novel analgesic omega-conotoxins from the vermivorous cone snail Conus moncuri provide new insights into the evolution of conopeptides.,Sousa SR, McArthur JR, Brust A, Bhola RF, Rosengren KJ, Ragnarsson L, Dutertre S, Alewood PF, Christie MJ, Adams DJ, Vetter I, Lewis RJ Sci Rep. 2018 Sep 7;8(1):13397. doi: 10.1038/s41598-018-31245-4. PMID:30194442^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.