Abstract
Cone snail venoms are considered a treasure trove of bioactive peptides. Despite over 800 species of cone snails being known, each producing over 1000 venom peptides, only about 150 unique venom peptides are structurally and functionally characterized. To overcome the limitations of the traditional low-throughput bio-discovery approaches, multi-omics systems approaches have been introduced to accelerate venom peptide discovery and characterisation. This “venomic” approach is starting to unravel the full complexity of cone snail venoms and to provide new insights into their biology and evolution. The main challenge for venomics is the effective integration of transcriptomics, proteomics, and pharmacological data and the efficient analysis of big datasets. Novel database search tools and visualisation techniques are now being introduced that facilitate data exploration, with ongoing advances in related omics fields being expected to further enhance venomics studies. Despite these challenges and future opportunities, cone snail venomics has already exponentially expanded the number of novel venom peptide sequences identified from the species investigated, although most novel conotoxins remain to be pharmacologically characterised. Therefore, efficient high-throughput peptide production systems and/or banks of miniaturized discovery assays are required to overcome this bottleneck and thus enhance cone snail venom bioprospecting and accelerate the identification of novel drug leads.
Highlights
Millions of years of evolution have generated natural products that can be successfully used as drugs and drug candidates, with >50% of all approved drugs arising from natural products or their derivatives [1]
Other conotoxins, including Xen2174 (Mr1A), a norepinephrine transporter antagonist isolated from the Conus marmoreus [6], CGX-1007 (Conantokin G), a N-methyl-D-aspartate (NMDA) receptor antagonist from Conus geographus [7], CGX-1051, a potassium channel blocker from Conus purpurascens [8], and ACV1 (Vc1.1) an AChR antagonist identified from Conus victoriae [9], have progressed into the clinic, only Xen2174 proved efficacious in patients
This review provides an overview of the impact of these technological advancements on cone snail venom research over the past decade and discusses the challenges and opportunities that remain
Summary
Millions of years of evolution have generated natural products that can be successfully used as drugs and drug candidates, with >50% of all approved drugs arising from natural products or their derivatives [1]. Advanced bio-engineering approaches are being used to improve the stability and oral bioavailability of peptides [24,25] In this context, cone snail venom peptides present an ideal source for the mining of potential drug candidates. Abundant peptides from common species such as C. geographus, Conus striatus, C. magus, Conus catus, C. purpurscens, and Conus textiles are most comprehensively studied, while the large pool of minor venom components remain mostly uncharacterized. Tapping into this peptide reserve requires a broader implementation of miniaturised high-throughput multidimensional strategies. This review provides an overview of the impact of these technological advancements on cone snail venom research over the past decade and discusses the challenges and opportunities that remain
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