“…Venomous snail neuropeptides, due to their chemical and biological diversity, coupled with high specificity, affinity, and molecular recognition, are fortuitous therapeutic resources for manipulating signaling in the nervous system 7 8 . In particular, Conoidean marine snails (cone snails, terebrids, and turrids) express disulfide-rich neuropeptides in their venom to subdue prey, requiring the peptides to be fast acting, efficient, and highly specific – all essential virtues of a successful drug candidate 9 10 11 . Ziconotide (ω-MVIIA), a 25 amino acid peptide expressed in the venom of cone snail Conus magus, is an analgesic therapy commercially approved in the US and Europe 12 .…”
The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB.
“…Venomous snail neuropeptides, due to their chemical and biological diversity, coupled with high specificity, affinity, and molecular recognition, are fortuitous therapeutic resources for manipulating signaling in the nervous system 7 8 . In particular, Conoidean marine snails (cone snails, terebrids, and turrids) express disulfide-rich neuropeptides in their venom to subdue prey, requiring the peptides to be fast acting, efficient, and highly specific – all essential virtues of a successful drug candidate 9 10 11 . Ziconotide (ω-MVIIA), a 25 amino acid peptide expressed in the venom of cone snail Conus magus, is an analgesic therapy commercially approved in the US and Europe 12 .…”
The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB.
“…Turripeptides function as neurotoxins modulating ion channels and causing disruption of the neuromuscular transmission, which leads to paralysis of prey ( Aguilar et al. 2009 ; Gonzales and Saloma 2014 ). One orthologous cluster including 4 turripeptide-like transcripts with the Kazal-domain characteristic of turripeptides was identified among the fireworm putative toxin genes.…”
Amphinomids, more commonly known as fireworms, are a basal lineage of marine annelids characterized by the presence of defensive dorsal calcareous chaetae, which break off upon contact. It has long been hypothesized that amphinomids are venomous and use the chaetae to inject a toxic substance. However, studies investigating fireworm venom from a morphological or molecular perspective are scarce and no venom gland has been identified to date, nor any toxin characterized at the molecular level. To investigate this question, we analyzed the transcriptomes of three species of fireworms—Eurythoe complanata, Hermodice carunculata, and Paramphinome jeffreysii—following a venomics approach to identify putative venom compounds. Our venomics pipeline involved de novo transcriptome assembly, open reading frame, and signal sequence prediction, followed by three different homology search strategies: BLAST, HMMER sequence, and HMMER domain. Following this pipeline, we identified 34 clusters of orthologous genes, representing 13 known toxin classes that have been repeatedly recruited into animal venoms. Specifically, the three species share a similar toxin profile with C-type lectins, peptidases, metalloproteinases, spider toxins, and CAP proteins found among the most highly expressed toxin homologs. Despite their great diversity, the putative toxins identified are predominantly involved in three major biological processes: hemostasis, inflammatory response, and allergic reactions, all of which are commonly disrupted after fireworm stings. Although the putative fireworm toxins identified here need to be further validated, our results strongly suggest that fireworms are venomous animals that use a complex mixture of toxins for defense against predators.
“…Other non- Conus Conoideans, such as the Turridae ( s.l. ) family, which has more recently been divided into seven family groups ( Tucker and Tenorio 2009 ; Bouchet et al 2011 ), and the Terebridae family, also produce venom ( Heralde et al 2008 ; Aguilar et al 2009 ; Gonzales and Saloma 2014 ; Gorson et al 2015 ; Moon et al 2016 ). Cone snails and terebrids dwell in shallow-water tropical marine habitats, while the majority of turrids can be found at greater depths (>200m; Taylor 1977 ).…”
Section: Characterizing Conoidean Venom Evolution and Variationmentioning
confidence: 99%
“…Terebrids and turrids (some less than 3 mm in length) have incredibly small venom ducts, producing limited amounts of venom, which initially inhibited their characterization. Using an integrated venomics strategy, venom research of terebrids and turrids has become more feasible ( Castelin et al 2012 ; Kendel et al 2013 ; Gonzales and Saloma 2014 ; Gorson et al 2015 ; Moon et al 2016 ). Fig.…”
Section: Characterizing Conoidean Venom Evolution and Variationmentioning
confidence: 99%
“…Conoidean venoms are a complex mixture of small molecules, peptides and proteins ( Norton and Olivera 2006 ; Gonzales and Saloma 2014 ; Gorson et al 2015 ; Neves et al 2015 ). Each Conoidean venom consists of >100 different peptides which contain a signal sequence, followed by a pro region, and a mature peptide at the C-terminus ( Olivera et al 1999 ; Lavergne et al 2015 ).…”
Section: Characterizing Conoidean Venom Evolution and Variationmentioning
Venomous organisms used in research were historically chosen based on size and availability. This opportunity-driven strategy created a species bias in which snakes, scorpions, and spiders became the primary subjects of venom research. Increasing technological advancements have enabled interdisciplinary studies using genomics, transcriptomics, and proteomics to expand venom investigation to animals that produce small amounts of venom or lack traditional venom producing organs. One group of non-traditional venomous organisms that have benefitted from the rise of -omic technologies is the Conoideans. The Conoidean superfamily of venomous marine snails includes, the Terebridae, Turridae (s.l), and Conidae. Conoidea venom is used for both predation and defense, and therefore under strong selection pressures. The need for conoidean venom peptides to be potent and specific to their molecular targets has made them important tools for investigating cellular physiology and bioactive compounds that are beneficial to improving human health. A convincing case for the potential of Conoidean venom is made with the first commercially available conoidean venom peptide drug Ziconotide (Prialt®), an analgesic derived from Conus magus venom that is used to treat chronic pain in HIV and cancer patients. Investigation of conoidean venom using -omics technology provides significant insights into predator-driven diversification in biodiversity and identifies novel compounds for manipulating cellular communication, especially as it pertains to disease and disorders.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
