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ABSTRACT
Introduction: Centipedes are one of the oldest and most successful lineages of venomous terrestrial predators. Despite their use for centuries in traditional medicine, centipede venoms remain poorly studied. However, recent work indicates that centipede venoms are highly complex chemical arsenals that are rich in disulfide-constrained peptides that have novel pharmacology and three-dimensional structure.
Areas covered: This review summarizes what is currently known about centipede venom proteins, with a focus on disulfide-rich peptides that have novel or unexpected pharmacology that might be useful from a therapeutic perspective. The authors also highlight the remarkable diversity of constrained three-dimensional peptide scaffolds present in these venoms that might be useful for bioengineering of drug leads.
Expert opinion: Like most arthropod predators, centipede venoms are rich in peptides that target neuronal ion channels and receptors, but it is also becoming increasingly apparent that many of these peptides have novel or unexpected pharmacological properties with potential applications in drug discovery and development.
Article highlights
Centipedes are one of the oldest and most successful lineages of venomous predators but studies of their venom have been restricted to only a handful of the 3500 extant species. Despite recent advances in understanding the molecular composition of centipede venoms, they remain underappreciated as a potential source of therapeutics despite their use in traditional medicine for many centuries.
The venom apparatus of centipedes that is markedly different to that of other venomous arthropods such as spiders and scorpions. Moreover, in comparison to arachnids, centipede venoms contain a higher proportion of protein toxins and a more structurally diverse repertoire of peptide toxins.
Centipede venoms contain an astonishing variety of peptide toxins that encompass a greater diversity of disulfide-constrained peptide scaffolds than reported in any other venom. Studies to date have already identified 19 families of disulfide-rich peptides that appear to be unique to centipede venom.
Despite the immense diversity of putatively unique three-dimensional peptide folds in centipede venom, structures are currently available for only two of the 19 novel peptide-toxin families. Future exploration of these novel venom peptides is likely to expand the repertoire of disulfide-stabilized structural templates suitable for bioengineering of drug leads and diagnostics.
Centipede venoms are rich in peptide toxins that inhibit presynaptic voltage-gated ion channels, as might be expected for a neurotoxic venom. However, these venoms also contain peptides with unexpected pharmacology, such as auxiliary subunit-mediated inhibition of KV7.1, activation of CaV channels, and even peptides with anti-thrombotic properties.
No centipede venom peptides have yet progressed to late-stage preclinical studies or clinical trials. However, the next decade promises to be a transformative period where fundamental investigations of centipede venom begin to be leveraged for drug discovery applications.
This box summarizes key points contained in the article.
Acknowledgments
The authors thank Jamie Vandenberg for comments on the manuscript.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.