Cone snail

Animal venoms and toxins hold promise as sources of novel drug candidates, therapeutic agents, and biomolecules. To fully harness their potential, it is crucial to develop reliable testing methods that provide a comprehensive understanding of their effects and mechanisms of action. However, traditional rodent assays encounter difficulties in mimicking venom-induced effects in human due to the impractical venom dosage levels. The search for reliable testing methods has led to the emergence of zebrafish ( Danio rerio ) as a versatile model organism for evaluating animal venoms and toxins...

OBJECTIVE: To investigate the population distribution of intermediate host snails and crabs of Paragonimus along the Jiulongjiang River, Zhangjiang River, and Dongxi River basins in Bopingling Mountain, southern Fujian Province, so as to provide baseline data for researches on parasitic disease prevention and control and enlargement of samples in the parasitic resource bank. METHODS: A total of 23 villages in 8 counties (districts) along the Jiulong River, Zhangjiang River, and Dongxi River basins in Zhangzhou City, Fujian Province were selected as survey sites during the period from November 2020 through March 2023, and snail and freshwater crabs were sampled from 1 to 3 streams and ditches neighboring residential areas in each village...

The venom of cone snails has been proven to be a rich source of bioactive peptides that target a variety of ion channels and receptors. α-Conotoxins (αCtx) interact with nicotinic acetylcholine receptors (nAChRs) and are powerful tools for investigating the structure and function of the various nAChR subtypes. By studying how conotoxins interact with nAChRs, we can improve our understanding of these receptors, leading to new insights into neurological diseases associated with nAChRs. Here, we describe the discovery and characterization of a novel conotoxin from Conus ateralbus , αCtx-AtIA, which has an amino acid sequence homologous to the well-described αCtx-PeIA, but with a different selectivity profile towards nAChRs...

We are entering an exciting time in structural biology where artificial intelligence can be used to predict protein structures with greater accuracy than ever before. Extending this level of accuracy to the predictions of disulfide-rich peptide structures is likely to be more challenging, at least in the short term, given the tight packing of cysteine residues and the numerous ways that the disulfide bonds can potentially be linked. It has been previously shown in many cases that several disulfide bond connectivities can be accommodated by a single set of NMR-derived structural data without significant violations...

Cone snails are carnivorous marine animals that prey on fish (piscivorous), worms (vermivorous), or other mollusks (molluscivorous). They produce a complex venom mostly made of disulfide-rich conotoxins and conopeptides in a compartmentalized venom gland. The pharmacology of cone snail venom has been increasingly investigated over more than half a century. The rising interest in cone snails was initiated by the surprising high human lethality rate caused by the defensive stings of some species. Although a vast amount of information has been uncovered on their venom composition, pharmacological targets, and mode of action of conotoxins, the venom-ecology relationships are still poorly understood for many lineages...

Okinawa prefecture is a popular tourist destination due to its beaches and reefs. The reefs host a large variety of animals, including a number of venomous species. Because of the popularity of the reefs and marine activities, people are frequently in close contact with dangerous venomous species and, thus, are exposed to potential envenomation. Commonly encountered venomous animals throughout Okinawa include the invertebrate cone snail, sea urchin, crown-of-thorns starfish, blue-ringed octopus, box jellyfish, and fire coral...

Cone snails possess a diverse array of novel peptide toxins, which selectively target ion channels and receptors in the nervous and cardiovascular systems. These numerous novel peptide toxins are a valuable resource for future marine drug development. In this review, we compared and analyzed the sequence diversity, three-dimensional structural variations, and evolutionary aspects of venom insulin derived from different cone snail species. The comparative analysis reveals that there are significant variations in the sequences and three-dimensional structures of venom insulins from cone snails with different feeding habits...

Venoms are primarily believed to evolve under strong diversifying selection resulting from persistent coevolution between predator and prey. Recent research has challenged this hypothesis, proposing that venoms from younger venomous lineages (e.g., snakes and cone snails) are governed predominantly by diversifying selection, while venoms from older venomous lineages (e.g., centipedes, scorpions, and spiders) are under stronger purifying selection. However, most research in older lineages has tested selection at more diverse phylogenetic scales...

The cysteine-free acyclic peptides present in marine cone snail venom have been much less investigated than their disulfide bonded counterparts. Precursor protein sequences derived from transcriptomic data, together with mass spectrometric fragmentation patterns for peptides present in venom duct tissue extracts, permit the identification of mature peptides. Twelve distinct gene superfamiles have been identified with precursor lengths between 64 and 158 residues. In the case of Conus monile, three distinct mature peptides have been identified, arising from two distinct protein precursors...

Conotoxins are toxic, disulfide-bond-rich peptides from cone snail venom that target a wide range of receptors and ion channels with multiple pathophysiological effects. Conotoxins have extraordinary potential for medical therapeutics that include cancer, microbial infections, epilepsy, autoimmune diseases, neurological conditions, and cardiovascular disorders. Despite the potential for these compounds in novel therapeutic treatment development, the process of identifying and characterizing the toxicities of conotoxins is difficult, costly, and time-consuming...

Venomous marine gastropods of the family Conidae are among the most diversified predators in marine realm-in large due to their complex venoms. Besides being a valuable source of bioactive neuropeptides conotoxins, cone-snails venoms are an excellent model for molecular evolution studies, addressing origin of key innovations. However, these studies are handicapped by scarce current knowledge on the tissues involved in venom production, as it is generally assumed the sole prerogative of the venom gland (VG)...

Nicotinic acetylcholine receptors (nAChRs) are drug targets for neurological diseases and disorders, but selective targeting of the large number of nAChR subtypes is challenging. Marine cone snail α-conotoxins are potent blockers of nAChRs and some have been engineered to achieve subtype selectivity. This engineering effort would benefit from rapid computational methods able to predict mutational energies, but current approaches typically require high-resolution experimental structures, which are not widely available for α-conotoxin complexes...

Climate change is affecting the distribution of marine organisms worldwide, including venomous marine gastropods that offer risks to human health, but also potential pharmacological resources, such as Conus sp. Species Distribution Models (SDMs) are valuable tools for predicting species distribution under climate change. The objective of our study was to evaluate the potential distribution of Conus geographus and C. textile in the Indo-Pacific region under different climate change scenarios for 2050 and 2090...

Parasitoid wasps are a diverse group of hymenopteran insects that serve as invaluable resources for pest biocontrol. To ensure successful parasitism, parasitoid wasps inject venom into their hosts to suppress their hosts' immunity, modulate hosts' development, metabolism, and even behavior. With over 600,000 estimated species, the diversity of parasitoid wasps surpasses that of other venomous animals, such as snakes, cone snails, and spiders. Parasitoid wasp venom is an underexplored source of bioactive molecules with potential applications in pest control and medicine...

Two novel redox conopeptides with proline residues outside and within the active site disulfide loop were derived from the venom duct transcriptome of the marine cone snails Conus frigidus and Conus amadis . Mature peptides with possible post-translational modification of 4-trans-hydroxylation of proline, namely, Fr874, Fr890[P1O], Fr890[P2O], Fr906, Am1038, and Am1054, have been chemically synthesized and characterized using mass spectrometry. The estimated reduction potential of cysteine disulfides of synthetic peptides varied from -298 to -328 mV, similar to the active site cysteine disulfide motifs of the redox family of proteins...

BACKGROUND: Genomes are powerful resources to understand the evolutionary mechanisms underpinning the origin and diversification of the venoms of cone snails (Conidae: Caenogastropoda) and could aid in the development of novel drugs. FINDINGS: Here, we used PacBio continuous long reads and Omni-C data to assemble the chromosome-level genome of Kalloconus canariensis, a vermivorous cone endemic to the Canary Islands. The final genome size was 2.87 Gb, with a N50 of 79...

Peptide hormones and neuropeptides form a diverse class of bioactive secreted molecules that control essential processes in animals. Despite breakthroughs in peptide discovery, many signaling peptides remain undiscovered. Recently, we demonstrated the use of somatostatin-mimicking toxins from cone snails to identify the invertebrate ortholog of somatostatin. Here, we show that this toxin-based approach can be systematically applied to discover other unknown secretory peptides that are likely to have signaling function...

Voltage-gated sodium (NaV ) channels are transmembrane proteins that play a critical role in electrical signaling in the nervous system and other excitable tissues. µ-Conotoxins are peptide toxins from the venoms of marine cone snails (genus Conus) that block NaV channels with nanomolar potency. Most species of the subgenera Textilia and Afonsoconus are difficult to acquire; therefore, their venoms have yet to be comprehensively interrogated for µ-conotoxins. The goal of this study was to find new µ-conotoxins from species of the subgenera Textilia and Afonsoconus and investigate their selectivity at human NaV channels...

Marine cone snails produce a wealth of peptide toxins (conotoxins) that bind their molecular targets with high selectivity and potency. Therefore, conotoxins constitute valuable biomolecular tools with a variety of biomedical purposes. The Mu8.1 conotoxin from Conus mucronatus is the founding member of the newly identified saposin-like conotoxin class of conotoxins and has been shown to target Cav2.3, a voltage-gated calcium channel. Two crystal structures have recently been determined of Mu8.1 at 2.3 and 2...

The cone snail Conus betulinus is a vermivorous species that is widely distributed in the South China Sea. Its crude venom contains various peptides used to prey on marine worms. In previous studies, a systematic analysis of the peptide toxin sequences from C. betulinus was carried out using a multiomics technique. In this study, 10 cysteine-free peptides that may possess insecticidal activity were selected from a previously constructed conopeptide library of C. betulinus using the CPY-Fe conopeptide as a template...