To see the other types of publications on this topic, follow the link: Venom toxins.
Journal articles on the topic 'Venom toxins'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Venom toxins.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Jaimes-Becerra, Adrian, Ranko Gacesa, Liam B. Doonan, Ashlie Hartigan, Antonio C. Marques, Beth Okamura, and Paul F. Long. "“Beyond Primary Sequence”—Proteomic Data Reveal Complex Toxins in Cnidarian Venoms." Integrative and Comparative Biology 59, no. 4 (July 8, 2019): 777–85. http://dx.doi.org/10.1093/icb/icz106.
Full textAbstract:
Abstract Venomous animals can deploy toxins for both predation and defense. These dual functions of toxins might be expected to promote the evolution of new venoms and alteration of their composition. Cnidarians are the most ancient venomous animals but our present understanding of their venom diversity is compromised by poor taxon sampling. New proteomic data were therefore generated to characterize toxins in venoms of a staurozoan, a hydrozoan, and an anthozoan. We then used a novel clustering approach to compare venom diversity in cnidarians to other venomous animals. Comparison of the presence or absence of 32 toxin protein families indicated venom composition did not vary widely among the 11 cnidarian species studied. Unsupervised clustering of toxin peptide sequences suggested that toxin composition of cnidarian venoms is just as complex as that in many venomous bilaterians, including marine snakes. The adaptive significance of maintaining a complex and relatively invariant venom remains unclear. Future study of cnidarian venom diversity, venom variation with nematocyst types and in different body regions are required to better understand venom evolution.
2
Schendel, Rash, Jenner, and Undheim. "The Diversity of Venom: The Importance of Behavior and Venom System Morphology in Understanding Its Ecology and Evolution." Toxins 11, no. 11 (November 14, 2019): 666. http://dx.doi.org/10.3390/toxins11110666.
Full textAbstract:
Venoms are one of the most convergent of animal traits known, and encompass a much greater taxonomic and functional diversity than is commonly appreciated. This knowledge gap limits the potential of venom as a model trait in evolutionary biology. Here, we summarize the taxonomic and functional diversity of animal venoms and relate this to what is known about venom system morphology, venom modulation, and venom pharmacology, with the aim of drawing attention to the importance of these largely neglected aspects of venom research. We find that animals have evolved venoms at least 101 independent times and that venoms play at least 11 distinct ecological roles in addition to predation, defense, and feeding. Comparisons of different venom systems suggest that morphology strongly influences how venoms achieve these functions, and hence is an important consideration for understanding the molecular evolution of venoms and their toxins. Our findings also highlight the need for more holistic studies of venom systems and the toxins they contain. Greater knowledge of behavior, morphology, and ecologically relevant toxin pharmacology will improve our understanding of the evolution of venoms and their toxins, and likely facilitate exploration of their potential as sources of molecular tools and therapeutic and agrochemical lead compounds.
3
Hu, Zhaotun, Bo Chen, Zhen Xiao, Xi Zhou, and Zhonghua Liu. "Transcriptomic Analysis of the Spider Venom Gland Reveals Venom Diversity and Species Consanguinity." Toxins 11, no. 2 (January 24, 2019): 68. http://dx.doi.org/10.3390/toxins11020068.
Full textAbstract:
Selenocosmia jiafu (S. jiafu) has been recently identified as a new species of spider in China. It lives in the same habitat as various other venomous spiders, including Chilobrachys jingzhao (C. jingzhao), Selenocosmia huwena (S. huwena), and Macrothele raveni (M. raveni). The venom from these different species of spiders exhibits some similarities and some differences in terms of their biochemical and electrophysiological properties. With the objective to illustrate the diversity in venom peptide toxins and to establish the evolutionary relationship between different spider species, we first performed transcriptomic analysis on a cDNA library from the venom gland of S. jiafu. We identified 146 novel toxin-like sequences, which were classified into eighteen different superfamilies. This transcriptome was then compared with that of C. jingzhao, which revealed that the putative toxins from both spider venoms may have originated from the same ancestor, although novel toxins evolved independently in the two species. A BLAST search and pharmacological analysis revealed that the two venoms have similar sodium channel modulation activity. This study provides insights into the venom of two closely related species of spider, which will prove useful towards understanding the structure and function of their toxins.
4
Xie, Chunfang, Laura-Oana Albulescu, Kristina B. M. Still, Julien Slagboom, Yumei Zhao, Zhengjin Jiang, Govert W. Somsen, Freek J. Vonk, Nicholas R. Casewell, and Jeroen Kool. "Varespladib Inhibits the Phospholipase A2 and Coagulopathic Activities of Venom Components from Hemotoxic Snakes." Biomedicines 8, no. 6 (June 17, 2020): 165. http://dx.doi.org/10.3390/biomedicines8060165.
Full textAbstract:
Phospholipase A2 (PLA2) enzymes are important toxins found in many snake venoms, and they can exhibit a variety of toxic activities including causing hemolysis and/or anticoagulation. In this study, the inhibiting effects of the small molecule PLA2 inhibitor varespladib on snake venom PLA2s was investigated by nanofractionation analytics, which combined chromatography, mass spectrometry (MS), and bioassays. The venoms of the medically important snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus, Echis ocellatus, and Oxyuranus scutellatus were separated by liquid chromatography (LC) followed by nanofractionation and interrogation of the fractions by a coagulation assay and a PLA2 assay. Next, we assessed the ability of varespladib to inhibit the activity of enzymatic PLA2s and the coagulopathic toxicities induced by fractionated snake venom toxins, and identified these bioactive venom toxins and those inhibited by varespladib by using parallel recorded LC-MS data and proteomics analysis. We demonstrated here that varespladib was not only capable of inhibiting the PLA2 activities of hemotoxic snake venoms, but can also effectively neutralize the coagulopathic toxicities (most profoundly anticoagulation) induced by venom toxins. While varespladib effectively inhibited PLA2 toxins responsible for anticoagulant effects, we also found some evidence that this inhibitory molecule can partially abrogate procoagulant venom effects caused by different toxin families. These findings further emphasize the potential clinical utility of varespladib in mitigating the toxic effects of certain snakebites.
5
Barua, Agneesh, and Alexander S. Mikheyev. "An ancient, conserved gene regulatory network led to the rise of oral venom systems." Proceedings of the National Academy of Sciences 118, no. 14 (March 29, 2021): e2021311118. http://dx.doi.org/10.1073/pnas.2021311118.
Full textAbstract:
Oral venom systems evolved multiple times in numerous vertebrates, enabling the exploitation of unique predatory niches. Yet how and when they evolved remains poorly understood. Up to now, most research on venom evolution has focused strictly on toxins. However, using toxins present in modern-day animals to trace the origin of the venom system is difficult, since they tend to evolve rapidly, show complex patterns of expression, and were incorporated into the venom arsenal relatively recently. Here we focus on gene regulatory networks associated with the production of toxins in snakes, rather than the toxins themselves. We found that overall venom gland gene expression was surprisingly well conserved when compared to salivary glands of other amniotes. We characterized the “metavenom network,” a network of ∼3,000 nonsecreted housekeeping genes that are strongly coexpressed with toxins and are primarily involved in protein folding and modification. Conserved across amniotes, this network was coopted for venom evolution by exaptation of existing members and the recruitment of new toxin genes. For instance, starting from this common molecular foundation, Heloderma lizards, shrews, and solenodon evolved venoms in parallel by overexpression of kallikreins, which were common in ancestral saliva and induce vasodilation when injected, causing circulatory shock. Derived venoms, such as those of snakes, incorporated novel toxins, though they still rely on hypotension for prey immobilization. These similarities suggest repeated cooption of shared molecular machinery for the evolution of oral venom in mammals and reptiles, blurring the line between truly venomous animals and their ancestors.
6
Walker, Andrew A. "The evolutionary dynamics of venom toxins made by insects and other animals." Biochemical Society Transactions 48, no. 4 (August 5, 2020): 1353–65. http://dx.doi.org/10.1042/bst20190820.
Full textAbstract:
Animal venoms are recognised as unique biological systems in which to study molecular evolution. Venom use has evolved numerous times among the insects, and insects today use venom to capture prey, defend themselves from predators, or to subdue and modulate host responses during parasitism. However, little is known about most insect venom toxins or the mode and tempo by which they evolve. Here, I review the evolutionary dynamics of insect venom toxins, and argue that insects offer many opportunities to examine novel aspects of toxin evolution. The key questions addressed are: How do venomous animals evolve from non-venomous animals, and how does this path effect the composition and pharmacology of the venom? What genetic processes (gene duplication, co-option, neofunctionalisation) are most important in toxin evolution? What kinds of selection pressures are acting on toxin-encoding genes and their cognate targets in envenomated animals? The emerging evidence highlights that venom composition and pharmacology adapts quickly in response to changing selection pressures resulting from new ecological interactions, and that such evolution occurs through a stunning variety of genetic mechanisms. Insects offer many opportunities to investigate the evolutionary dynamics of venom toxins due to their evolutionary history rich in venom-related adaptations, and their quick generation time and suitability for culture in the laboratory.
7
Kunalan, Sugita, Iekhsan Othman, Sharifah Syed Hassan, and Wayne Hodgson. "Proteomic Characterization of Two Medically Important Malaysian Snake Venoms, Calloselasma rhodostoma (Malayan Pit Viper) and Ophiophagus hannah (King Cobra)." Toxins 10, no. 11 (October 26, 2018): 434. http://dx.doi.org/10.3390/toxins10110434.
Full textAbstract:
Calloselasma rhodostoma (CR) and Ophiophagus hannah (OH) are two medically important snakes found in Malaysia. While some studies have described the biological properties of these venoms, feeding and environmental conditions also influence the concentration and distribution of snake venom toxins, resulting in variations in venom composition. Therefore, a combined proteomic approach using shotgun and gel filtration chromatography, analyzed by tandem mass spectrometry, was used to examine the composition of venoms from these Malaysian snakes. The analysis revealed 114 proteins (15 toxin families) and 176 proteins (20 toxin families) in Malaysian Calloselasma rhodostoma and Ophiophagus hannah species, respectively. Flavin monoamine oxidase, phospholipase A2, phosphodiesterase, snake venom metalloproteinase, and serine protease toxin families were identified in both venoms. Aminopeptidase, glutaminyl-peptide cyclotransferase along with ankyrin repeats were identified for the first time in CR venom, and insulin, c-type lectins/snaclecs, hepatocyte growth factor, and macrophage colony-stimulating factor together with tumor necrosis factor were identified in OH venom for the first time. Our combined proteomic approach has identified a comprehensive arsenal of toxins in CR and OH venoms. These data may be utilized for improved antivenom production, understanding pathological effects of envenoming, and the discovery of biologically active peptides with medical and/or biotechnological value.
8
Fidelis Bekeh Ada, Kenneth Igbang Sunday, and Emmanuel Akomaye Ugbong. "Animal venoms." GSC Biological and Pharmaceutical Sciences 14, no. 1 (January 30, 2021): 047–54. http://dx.doi.org/10.30574/gscbps.2021.14.1.0371.
Full textAbstract:
Venoms are poisons or toxins of animal origin in which the animal that produce the toxins are capable of introducing the toxins into the body of the victims. Animals that produce toxins but lack the ability to introduce the toxins into their victims are said to be poisonous animals. Venoms are classified based on their site of action in the bodies of their victims. Thus, they classified into local, auto pharmacological, antihaemostic, neurological mascular cardiac and renal types; and based on the type of animal producing the venom, it is difficult to classify venom based on chemical constitution because of the fact that a particular venom is highly complex chemically with many reactive sites. The role venoms play on organisms in the environment is highlighted.
9
Kazandjian, Taline D., Arif Arrahman, Kristina B. M. Still, Govert W. Somsen, Freek J. Vonk, Nicholas R. Casewell, Mark C. Wilkinson, and Jeroen Kool. "Anticoagulant Activity of Naja nigricollis Venom Is Mediated by Phospholipase A2 Toxins and Inhibited by Varespladib." Toxins 13, no. 5 (April 23, 2021): 302. http://dx.doi.org/10.3390/toxins13050302.
Full textAbstract:
Bites from elapid snakes typically result in neurotoxic symptoms in snakebite victims. Neurotoxins are, therefore, often the focus of research relating to understanding the pathogenesis of elapid bites. However, recent evidence suggests that some elapid snake venoms contain anticoagulant toxins which may help neurotoxic components spread more rapidly. This study examines the effects of venom from the West African black-necked spitting cobra (Naja nigricollis) on blood coagulation and identifies potential coagulopathic toxins. An integrated RPLC-MS methodology, coupled with nanofractionation, was first used to separate venom components, followed by MS, proteomics and coagulopathic bioassays. Coagulation assays were performed on both crude and nanofractionated N. nigricollis venom toxins as well as PLA2s and 3FTx purified from the venom. Assays were then repeated with the addition of either the phospholipase A2 inhibitor varespladib or the snake venom metalloproteinase inhibitor marimastat to assess whether either toxin inhibitor is capable of neutralizing coagulopathic venom activity. Subsequent proteomic analysis was performed on nanofractionated bioactive venom toxins using tryptic digestion followed by nanoLC-MS/MS measurements, which were then identified using Swiss-Prot and species-specific database searches. Varespladib, but not marimastat, was found to significantly reduce the anticoagulant activity of N. nigricollis venom and MS and proteomics analyses confirmed that the anticoagulant venom components mostly consisted of PLA2 proteins. We, therefore, conclude that PLA2s are the most likely candidates responsible for anticoagulant effects stimulated by N. nigricollis venom.
10
Modahl, Cassandra M., Rajeev Kungur Brahma, Cho Yeow Koh, Narumi Shioi, and R. Manjunatha Kini. "Omics Technologies for Profiling Toxin Diversity and Evolution in Snake Venom: Impacts on the Discovery of Therapeutic and Diagnostic Agents." Annual Review of Animal Biosciences 8, no. 1 (February 15, 2020): 91–116. http://dx.doi.org/10.1146/annurev-animal-021419-083626.
Full textAbstract:
Snake venoms are primarily composed of proteins and peptides, and these toxins have developed high selectivity to their biological targets. This makes venoms interesting for exploration into protein evolution and structure–function relationships. A single venom protein superfamily can exhibit a variety of pharmacological effects; these variations in activity originate from differences in functional sites, domains, posttranslational modifications, and the formations of toxin complexes. In this review, we discuss examples of how the major venom protein superfamilies have diversified, as well as how newer technologies in the omics fields, such as genomics, transcriptomics, and proteomics, can be used to characterize both known and unknown toxins.Because toxins are bioactive molecules with a rich diversity of activities, they can be useful as therapeutic and diagnostic agents, and successful examples of toxin applications in these areas are also reviewed. With the current rapid pace of technology, snake venom research and its applications will only continue to expand.
11
Klompen, Anna M. L., Jason Macrander, Adam M. Reitzel, and Sérgio N. Stampar. "Transcriptomic Analysis of Four Cerianthid (Cnidaria, Ceriantharia) Venoms." Marine Drugs 18, no. 8 (August 5, 2020): 413. http://dx.doi.org/10.3390/md18080413.
Full textAbstract:
Tube anemones, or cerianthids, are a phylogenetically informative group of cnidarians with complex life histories, including a pelagic larval stage and tube-dwelling adult stage, both known to utilize venom in stinging-cell rich tentacles. Cnidarians are an entirely venomous group that utilize their proteinaceous-dominated toxins to capture prey and defend against predators, in addition to several other ecological functions, including intraspecific interactions. At present there are no studies describing the venom for any species within cerianthids. Given their unique development, ecology, and distinct phylogenetic-placement within Cnidaria, our objective is to evaluate the venom-like gene diversity of four species of cerianthids from newly collected transcriptomic data. We identified 525 venom-like genes between all four species. The venom-gene profile for each species was dominated by enzymatic protein and peptide families, which is consistent with previous findings in other cnidarian venoms. However, we found few toxins that are typical of sea anemones and corals, and furthermore, three of the four species express toxin-like genes closely related to potent pore-forming toxins in box jellyfish. Our study is the first to provide a survey of the putative venom composition of cerianthids and contributes to our general understanding of the diversity of cnidarian toxins.
12
Undheim, Eivind A. B., Brett R. Hamilton, Nyoman D. Kurniawan, Greg Bowlay, Bronwen W. Cribb, David J. Merritt, Bryan G. Fry, Glenn F. King, and Deon J. Venter. "Production and packaging of a biological arsenal: Evolution of centipede venoms under morphological constraint." Proceedings of the National Academy of Sciences 112, no. 13 (March 16, 2015): 4026–31. http://dx.doi.org/10.1073/pnas.1424068112.
Full textAbstract:
Venom represents one of the most extreme manifestations of a chemical arms race. Venoms are complex biochemical arsenals, often containing hundreds to thousands of unique protein toxins. Despite their utility for prey capture, venoms are energetically expensive commodities, and consequently it is hypothesized that venom complexity is inversely related to the capacity of a venomous animal to physically subdue prey. Centipedes, one of the oldest yet least-studied venomous lineages, appear to defy this rule. Although scutigeromorph centipedes produce less complex venom than those secreted by scolopendrid centipedes, they appear to rely heavily on venom for prey capture. We show that the venom glands are large and well developed in both scutigerid and scolopendrid species, but that scutigerid forcipules lack the adaptations that allow scolopendrids to inflict physical damage on prey and predators. Moreover, we reveal that scolopendrid venom glands have evolved to accommodate a much larger number of secretory cells and, by using imaging mass spectrometry, we demonstrate that toxin production is heterogeneous across these secretory units. We propose that the differences in venom complexity between centipede orders are largely a result of morphological restrictions of the venom gland, and consequently there is a strong correlation between the morphological and biochemical complexity of this unique venom system. The current data add to the growing body of evidence that toxins are not expressed in a spatially homogenous manner within venom glands, and they suggest that the link between ecology and toxin evolution is more complex than previously thought.
13
Forster, Yvonne M., Silvan Reusser, Florian Forster, Stefan Bienz, and Laurent Bigler. "VenoMS—A Website for the Low Molecular Mass Compounds in Spider Venoms." Metabolites 10, no. 8 (August 11, 2020): 327. http://dx.doi.org/10.3390/metabo10080327.
Full textAbstract:
Spider venoms are highly complex mixtures. Numerous spider venom metabolites are uniquely found in spider venoms and are of interest concerning their potential use in pharmacology, agriculture, and cosmetics. A nontargeted ultra-high performance high-resolution electrospray tandem mass spectrometry (UHPLC-HR-ESI-MS/MS) approach offers a resource-saving way for the analysis of crude spider venom. However, the identification of known as well as the structure elucidation of unknown low molecular mass spider venom compounds based on their MS/MS spectra is challenging because (1) acylpolyamine toxins are exclusively found in spider and wasp venom, (2) reference MS/MS spectra are missing in established mass spectrometry databases, and (3) trivial names for the various toxin metabolites are used in an inconsistent way in literature. Therefore, we introduce the freely accessible MS website for low molecular mass spider venom metabolites, venoMS, containing structural information, MS/MS spectra, and links to related literature. Currently the database contains the structures of 409 acylpolyamine toxins, 36 free linear polyamines, and 81 additional spider venom metabolites. Implemented into this website is a fragment ion calculator (FRIOC) that allows us to predict fragment ions of linear polyamine derivatives. With three metabolites from the venom of the spider Agelenopsis aperta, it was demonstrated how the new website can support the structural elucidation of acylpolyamines using their MS/MS spectra.
14
Chaves-Moreira, Daniele, Fernando Hitomi Matsubara, Zelinda Schemczssen-Graeff, Elidiana De Bona, Vanessa Ribeiro Heidemann, Clara Guerra-Duarte, Luiza Helena Gremski, et al. "Brown Spider (Loxosceles) Venom Toxins as Potential Biotools for the Development of Novel Therapeutics." Toxins 11, no. 6 (June 19, 2019): 355. http://dx.doi.org/10.3390/toxins11060355.
Full textAbstract:
Brown spider envenomation results in dermonecrosis with gravitational spreading characterized by a marked inflammatory reaction and with lower prevalence of systemic manifestations such as renal failure and hematological disturbances. Several toxins make up the venom of these species, and they are mainly peptides and proteins ranging from 5–40 kDa. The venoms have three major families of toxins: phospholipases-D, astacin-like metalloproteases, and the inhibitor cystine knot (ICK) peptides. Serine proteases, serpins, hyaluronidases, venom allergens, and a translationally controlled tumor protein (TCTP) are also present. Toxins hold essential biological properties that enable interactions with a range of distinct molecular targets. Therefore, the application of toxins as research tools and clinical products motivates repurposing their uses of interest. This review aims to discuss possibilities for brown spider venom toxins as putative models for designing molecules likely for therapeutics based on the status quo of brown spider venoms. Herein, we explore new possibilities for the venom components in the context of their biochemical and biological features, likewise their cellular targets, three-dimensional structures, and mechanisms of action.
15
Silva, Anjana, and Geoffrey K. Isbister. "Current research into snake antivenoms, their mechanisms of action and applications." Biochemical Society Transactions 48, no. 2 (March 20, 2020): 537–46. http://dx.doi.org/10.1042/bst20190739.
Full textAbstract:
Snakebite is a major public health issue in the rural tropics. Antivenom is the only specific treatment currently available. We review the history, mechanism of action and current developments in snake antivenoms. In the late nineteenth century, snake antivenoms were first developed by raising hyperimmune serum in animals, such as horses, against snake venoms. Hyperimmune serum was then purified to produce whole immunoglobulin G (IgG) antivenoms. IgG was then fractionated to produce F(ab) and F(ab′)2 antivenoms to reduce adverse reactions and increase efficacy. Current commercial antivenoms are polyclonal mixtures of antibodies or their fractions raised against all toxin antigens in a venom(s), irrespective of clinical importance. Over the last few decades there have been small incremental improvements in antivenoms, to make them safer and more effective. A number of recent developments in biotechnology and toxinology have contributed to this. Proteomics and transcriptomics have been applied to venom toxin composition (venomics), improving our understanding of medically important toxins. In addition, it has become possible to identify toxins that contain epitopes recognized by antivenom molecules (antivenomics). Integration of the toxinological profile of a venom and its composition to identify medically relevant toxins improved this. Furthermore, camelid, humanized and fully human monoclonal antibodies and their fractions, as well as enzyme inhibitors have been experimentally developed against venom toxins. Translation of such technology into commercial antivenoms requires overcoming the high costs, limited knowledge of venom and antivenom pharmacology, and lack of reliable animal models. Addressing such should be the focus of antivenom research.
16
Mahmood, Hamid, Nazar Afaridi, Abdullah Mashoori, Ammara Waqar, and Mujadid-ur Rehman. "SNAKE VENOM." Professional Medical Journal 21, no. 01 (December 5, 2018): 130–35. http://dx.doi.org/10.29309/tpmj/2014.21.01.1912.
Full textAbstract:
Introduction: Viperidae venoms contain toxins that are direct or indirectanticoagulants that inhibit the clotting pathway, therefore increasing the risk of bleeding. Severalvenoms from the families Viperidae contain proteolytic enzymes that exercise some effect on theblood coagulation process. Snake venom toxins which delay blood coagulation are proteins orglycoprotein with molecular weights ranging from 6 kDa to 350 kDa. These factors inhibit bloodcoagulation by different mechanisms.Some snake venoms contain toxins that are direct orindirect anticoagulants, which inhibit the clotting process, thus increasing the risk of bleeding.Snake venom toxins that prolong blood coagulation are proteins or glycoproteins with molecularmasses ranging from 6 to 350 kDa. Methods: The crude venom of E. carinatuswas obtained fromthe Venomous Animals from department of microbiology Hazara University, Mansehra(Pakistan). Sephadex G-75 and DEAE-Sepharose columns were purchased from Pharmacia(Sweden). CaCl2 and PT kit was purchased from Fisher Diagnostics (USA). Protein markers wereobtained from BioRad (Hercules, USA). Other reagents and chemicals were of analytical gradefrom Fluka and Merck. Results: The anticoagulant fractions (F2C and F2D) isolated in thepresent work were characterized as proteases, since a photolytic effect was observed on casein,BAPNA or human plasma. Our results showed that the PT value significantly increased in the F2Cand F2D fractions as compared with PT value of the crude venom. Conclusions: Inthe presentstudy, the venom of Echiscarinatuswas fractionated by chromatography and each fractionevaluated by PT test. These fractions showed enzymatic activity. Their main components wereproteins of molecular weights of about 42, 50 and 79 kDa. . Further studies are needed to verifythis hypothesis.
17
Babenko, Vladislav V., Rustam H. Ziganshin, Christoph Weise, Igor Dyachenko, Elvira Shaykhutdinova, Arkady N. Murashev, Maxim Zhmak, et al. "Novel Bradykinin-Potentiating Peptides and Three-Finger Toxins from Viper Venom: Combined NGS Venom Gland Transcriptomics and Quantitative Venom Proteomics of the Azemiops feae Viper." Biomedicines 8, no. 8 (July 28, 2020): 249. http://dx.doi.org/10.3390/biomedicines8080249.
Full textAbstract:
Feae’s viper Azemipos feae belongs to the Azemiopinae subfamily of the Viperidae family. The effects of Viperidae venoms are mostly coagulopathic with limited neurotoxicity manifested by phospholipases A2. From A. feae venom, we have earlier isolated azemiopsin, a novel neurotoxin inhibiting the nicotinic acetylcholine receptor. To characterize other A. feae toxins, we applied label-free quantitative proteomics, which revealed 120 unique proteins, the most abundant being serine proteinases and phospholipases A2. In total, toxins representing 14 families were identified, among which bradykinin-potentiating peptides with unique amino acid sequences possessed biological activity in vivo. The proteomic analysis revealed also basal (commonly known as non-conventional) three-finger toxins belonging to the group of those possessing neurotoxic activity. This is the first indication of the presence of three-finger neurotoxins in viper venom. In parallel, the transcriptomic analysis of venom gland performed by Illumina next-generation sequencing further revealed 206 putative venom transcripts. Together, the study unveiled the venom proteome and venom gland transciptome of A. feae, which in general resemble those of other snakes from the Viperidae family. However, new toxins not found earlier in viper venom and including three-finger toxins and unusual bradykinin-potentiating peptides were discovered.
18
Madio, Bruno, Glenn F. King, and Eivind A. B. Undheim. "Sea Anemone Toxins: A Structural Overview." Marine Drugs 17, no. 6 (June 1, 2019): 325. http://dx.doi.org/10.3390/md17060325.
Full textAbstract:
Sea anemones produce venoms of exceptional molecular diversity, with at least 17 different molecular scaffolds reported to date. These venom components have traditionally been classified according to pharmacological activity and amino acid sequence. However, this classification system suffers from vulnerabilities due to functional convergence and functional promiscuity. Furthermore, for most known sea anemone toxins, the exact receptors they target are either unknown, or at best incomplete. In this review, we first provide an overview of the sea anemone venom system and then focus on the venom components. We have organised the venom components by distinguishing firstly between proteins and non-proteinaceous compounds, secondly between enzymes and other proteins without enzymatic activity, then according to the structural scaffold, and finally according to molecular target.
19
Lu, Aiping, Maren Watkins, Qing Li, Samuel D. Robinson, Gisela P. Concepcion, Mark Yandell, Zhiping Weng, Baldomero M. Olivera, Helena Safavi-Hemami, and Alexander E. Fedosov. "Transcriptomic Profiling Reveals Extraordinary Diversity of Venom Peptides in Unexplored Predatory Gastropods of the Genus Clavus." Genome Biology and Evolution 12, no. 5 (April 23, 2020): 684–700. http://dx.doi.org/10.1093/gbe/evaa083.
Full textAbstract:
Abstract Predatory gastropods of the superfamily Conoidea number over 12,000 living species. The evolutionary success of this lineage can be explained by the ability of conoideans to produce complex venoms for hunting, defense, and competitive interactions. Whereas venoms of cone snails (family Conidae) have become increasingly well studied, the venoms of most other conoidean lineages remain largely uncharacterized. In the present study, we present the venom gland transcriptomes of two species of the genus Clavus that belong to the family Drilliidae. Venom gland transcriptomes of two specimens of Clavus canalicularis and two specimens of Clavus davidgilmouri were analyzed, leading to the identification of a total of 1,176 putative venom peptide toxins (drillipeptides). Based on the combined evidence of secretion signal sequence identity, entire precursor similarity search (BLAST), and the orthology inference, putative Clavus toxins were assigned to 158 different gene families. The majority of identified transcripts comprise signal, pro-, mature peptide, and post-regions, with a typically short (<50 amino acids) and cysteine-rich mature peptide region. Thus, drillipeptides are structurally similar to conotoxins. However, convincing homology with known groups of Conus toxins was only detected for very few toxin families. Among these are Clavus counterparts of Conus venom insulins (drillinsulins), porins (drilliporins), and highly diversified lectins (drillilectins). The short size of most drillipeptides and structural similarity to conotoxins were unexpected, given that most related conoidean gastropod families (Terebridae and Turridae) possess longer mature peptide regions. Our findings indicate that, similar to conotoxins, drillipeptides may represent a valuable resource for future pharmacological exploration.
20
Rokyta, Darin R., Mark J. Margres, Micaiah J. Ward, and Elda E. Sanchez. "The genetics of venom ontogeny in the eastern diamondback rattlesnake (Crotalus adamanteus)." PeerJ 5 (April 27, 2017): e3249. http://dx.doi.org/10.7717/peerj.3249.
Full textAbstract:
The same selective forces that give rise to rapid inter- and intraspecific divergence in snake venoms can also favor differences in venoms across life-history stages. Ontogenetic changes in venom composition are well known and widespread in snakes but have not been investigated to the level of unambiguously identifying the specific loci involved. The eastern diamondback rattlesnake was previously shown to undergo an ontogenetic shift in venom composition at sexual maturity, and this shift accounted for more venom variation than geography. To characterize the genetics underlying the ontogenetic venom compositional change in C. adamanteus, we sequenced adult/juvenile pairs of venom-gland transcriptomes from five populations previously shown to have different adult venom compositions. We identified a total of 59 putative toxin transcripts for C. adamanteus, and 12 of these were involved in the ontogenetic change. Three toxins were downregulated, and nine were upregulated in adults relative to juveniles. Adults and juveniles expressed similar total levels of snake-venom metalloproteinases but differed substantially in their featured paralogs, and adults expressed higher levels of Bradykinin-potentiating and C-type natriuretic peptides, nerve growth factor, and specific paralogs of phospholipases A2 and snake venom serine proteinases. Juvenile venom was more toxic to mice, indicating that the expression differences resulted in a phenotypically, and therefore potentially ecologically, significant difference in venom function. We also showed that adult and juvenile venom-gland transcriptomes for a species with known ontogenetic venom variation were equally effective at individually providing a full characterization of the venom genes of a species but that any particular individual was likely to lack several toxins in their transcriptome. A full characterization of a species’ venom-gene complement therefore requires sequencing more than one individual, although the ages of the individuals are unimportant.
21
Tan, Kae Yi, Choo Hock Tan, Lawan Chanhome, and Nget Hong Tan. "Comparative venom gland transcriptomics ofNaja kaouthia(monocled cobra) from Malaysia and Thailand: elucidating geographical venom variation and insights into sequence novelty." PeerJ 5 (April 5, 2017): e3142. http://dx.doi.org/10.7717/peerj.3142.
Full textAbstract:
BackgroundThe monocled cobra (Naja kaouthia) is a medically important venomous snake in Southeast Asia. Its venom has been shown to vary geographically in relation to venom composition and neurotoxic activity, indicating vast diversity of the toxin genes within the species. To investigate the polygenic trait of the venom and its locale-specific variation, we profiled and compared the venom gland transcriptomes ofN. kaouthiafrom Malaysia (NK-M) and Thailand (NK-T) applying next-generation sequencing (NGS) technology.MethodsThe transcriptomes were sequenced on the Illumina HiSeq platform, assembled and followed by transcript clustering and annotations for gene expression and function. Pairwise or multiple sequence alignments were conducted on the toxin genes expressed. Substitution rates were studied for the major toxins co-expressed in NK-M and NK-T.Results and discussionThe toxin transcripts showed high redundancy (41–82% of the total mRNA expression) and comprised 23 gene families expressed in NK-M and NK-T, respectively (22 gene families were co-expressed). Among the venom genes, three-finger toxins (3FTxs) predominated in the expression, with multiple sequences noted. Comparative analysis and selection study revealed that 3FTxs are genetically conserved between the geographical specimens whilst demonstrating distinct differential expression patterns, implying gene up-regulation for selected principal toxins, or alternatively, enhanced transcript degradation or lack of transcription of certain traits. One of the striking features that elucidates the inter-geographical venom variation is the up-regulation of α-neurotoxins (constitutes ∼80.0% of toxin’s fragments per kilobase of exon model per million mapped reads (FPKM)), particularly the long-chain α-elapitoxin-Nk2a (48.3%) in NK-T but only 1.7% was noted in NK-M. Instead, short neurotoxin isoforms were up-regulated in NK-M (46.4%). Another distinct transcriptional pattern observed is the exclusively and abundantly expressed cytotoxin CTX-3 in NK-T. The findings suggested correlation with the geographical variation in proteome and toxicity of the venom, and support the call for optimising antivenom production and use in the region. Besides, the current study uncovered full and partial sequences of numerous toxin genes fromN. kaouthiawhich have not been reported hitherto; these includeN. kaouthia-specificl-amino acid oxidase (LAAO), snake venom serine protease (SVSP), cystatin, acetylcholinesterase (AChE), hyaluronidase (HYA), waprin, phospholipase B (PLB), aminopeptidase (AP), neprilysin, etc. Taken together, the findings further enrich the snake toxin database and provide deeper insights into the genetic diversity of cobra venom toxins.
22
Hartigan, Ashlie, Adrian Jaimes-Becerra, Beth Okamura, Liam B. Doonan, Malcolm Ward, Antonio C. Marques, and Paul F. Long. "Recruitment of toxin-like proteins with ancestral venom function supports endoparasitic lifestyles of Myxozoa." PeerJ 9 (April 26, 2021): e11208. http://dx.doi.org/10.7717/peerj.11208.
Full textAbstract:
Cnidarians are the oldest lineage of venomous animals and use nematocysts to discharge toxins. Whether venom toxins have been recruited to support parasitic lifestyles in the Endocnidozoa (Myxozoa + Polypodium) is, however, unknown. To examine this issue we variously employed transcriptomic, proteomic, associated molecular phylogenies, and localisation studies on representative primitive and derived myxozoans (Malacosporea and Myxosporea, respectively), Polypodium hydriforme, and the free-living staurozoan Calvadosia cruxmelitensis. Our transcriptomics and proteomics analyses provide evidence for expression and translation of venom toxin homologs in myxozoans. Phylogenetic placement of Kunitz type serine protease inhibitors and phospholipase A2 enzymes reveals modification of toxins inherited from ancestral free-living cnidarian toxins, and that venom diversity is reduced in myxozoans concordant with their reduced genome sizes. Various phylogenetic analyses of the Kunitz-type toxin family in Endocnidozoa suggested lineage-specific gene duplications, which offers a possible mechanism for enhancing toxin diversification. Toxin localisation in the malacosporean Buddenbrockia plumatellae substantiates toxin translation and thus illustrates a repurposing of toxin function for endoparasite development and interactions with hosts, rather than for prey capture or defence. Whether myxozoan venom candidates are expressed in transmission stages (e.g. in nematocysts or secretory vesicles) requires further investigation.
23
Jenner, Ronald A., Bjoern M. von Reumont, Lahcen I. Campbell, and Eivind A. B. Undheim. "Parallel Evolution of Complex Centipede Venoms Revealed by Comparative Proteotranscriptomic Analyses." Molecular Biology and Evolution 36, no. 12 (August 8, 2019): 2748–63. http://dx.doi.org/10.1093/molbev/msz181.
Full textAbstract:
Abstract Centipedes are among the most ancient groups of venomous predatory arthropods. Extant species belong to five orders, but our understanding of the composition and evolution of centipede venoms is based almost exclusively on one order, Scolopendromorpha. To gain a broader and less biased understanding we performed a comparative proteotranscriptomic analysis of centipede venoms from all five orders, including the first venom profiles for the orders Lithobiomorpha, Craterostigmomorpha, and Geophilomorpha. Our results reveal an astonishing structural diversity of venom components, with 93 phylogenetically distinct protein and peptide families. Proteomically-annotated gene trees of these putative toxin families show that centipede venom composition is highly dynamic across macroevolutionary timescales, with numerous gene duplications as well as functional recruitments and losses of toxin gene families. Strikingly, not a single family is found in the venoms of representatives of all five orders, with 67 families being unique for single orders. Ancestral state reconstructions reveal that centipede venom originated as a simple cocktail comprising just four toxin families, with very little compositional evolution happening during the approximately 50 My before the living orders had diverged. Venom complexity then increased in parallel within the orders, with scolopendromorphs evolving particularly complex venoms. Our results show that even venoms composed of toxins evolving under the strong constraint of negative selection can have striking evolutionary plasticity on the compositional level. We show that the functional recruitments and losses of toxin families that shape centipede venom arsenals are not concentrated early in their evolutionary history, but happen frequently throughout.
24
Yang, Shilong, Yunfei Wang, Lu Wang, Peter Kamau, Hao Zhang, Anna Luo, Xiancui Lu, and Ren Lai. "Target switch of centipede toxins for antagonistic switch." Science Advances 6, no. 32 (August 2020): eabb5734. http://dx.doi.org/10.1126/sciadv.abb5734.
Full textAbstract:
Animal venoms are powerful, highly evolved chemical weapons for defense and predation. While venoms are used mainly to lethally antagonize heterospecifics (individuals of a different species), nonlethal envenomation of conspecifics (individuals of the same species) is occasionally observed. Both the venom and target specifications underlying these two forms of envenomation are still poorly understood. Here, we show a target-switching mechanism in centipede (Scolopendra subspinipes) venom. On the basis of this mechanism, a major toxin component [Ssm Spooky Toxin (SsTx)] in centipede venom inhibits the Shal channel in conspecifics but not in heterospecifics to cause short-term, recoverable, and nonlethal envenomation. This same toxin causes fatal heterospecific envenomation, for example, by switching its target to the Shaker channels in heterospecifics without inhibiting the Shaker channel of conspecific S. subspinipes individuals. These findings suggest that venom components exhibit intricate coevolution with their targets in both heterospecifics and conspecifics, which enables a single toxin to develop graded intraspecific and interspecific antagonistic interactions.
25
Mitpuangchon, Natrada, Kwan Nualcharoen, Singtoe Boonrotpong, and Patamarerk Engsontia. "Identification of Novel Toxin Genes from the Stinging Nettle Caterpillar Parasa lepida (Cramer, 1799): Insights into the Evolution of Lepidoptera Toxins." Insects 12, no. 5 (April 29, 2021): 396. http://dx.doi.org/10.3390/insects12050396.
Full textAbstract:
Many animal species can produce venom for defense, predation, and competition. The venom usually contains diverse peptide and protein toxins, including neurotoxins, proteolytic enzymes, protease inhibitors, and allergens. Some drugs for cancer, neurological disorders, and analgesics were developed based on animal toxin structures and functions. Several caterpillar species possess venoms that cause varying effects on humans both locally and systemically. However, toxins from only a few species have been investigated, limiting the full understanding of the Lepidoptera toxin diversity and evolution. We used the RNA-seq technique to identify toxin genes from the stinging nettle caterpillar, Parasa lepida (Cramer, 1799). We constructed a transcriptome from caterpillar urticating hairs and reported 34,968 unique transcripts. Using our toxin gene annotation pipeline, we identified 168 candidate toxin genes, including protease inhibitors, proteolytic enzymes, and allergens. The 21 P. lepida novel Knottin-like peptides, which do not show sequence similarity to any known peptide, have predicted 3D structures similar to tarantula, scorpion, and cone snail neurotoxins. We highlighted the importance of convergent evolution in the Lepidoptera toxin evolution and the possible mechanisms. This study opens a new path to understanding the hidden diversity of Lepidoptera toxins, which could be a fruitful source for developing new drugs.
26
Rodrigo, Ana P., Ana R. Grosso, Pedro V. Baptista, Alexandra R. Fernandes, and Pedro M. Costa. "A Transcriptomic Approach to the Recruitment of Venom Proteins in a Marine Annelid." Toxins 13, no. 2 (January 28, 2021): 97. http://dx.doi.org/10.3390/toxins13020097.
Full textAbstract:
The growing number of known venomous marine invertebrates indicates that chemical warfare plays an important role in adapting to diversified ecological niches, even though it remains unclear how toxins fit into the evolutionary history of these animals. Our case study, the Polychaeta Eulalia sp., is an intertidal predator that secretes toxins. Whole-transcriptome sequencing revealed proteinaceous toxins secreted by cells in the proboscis and delivered by mucus. Toxins and accompanying enzymes promote permeabilization, coagulation impairment and the blocking of the neuromuscular activity of prey upon which the worm feeds by sucking pieces of live flesh. The main neurotoxins (“phyllotoxins”) were found to be cysteine-rich proteins, a class of substances ubiquitous among venomous animals. Some toxins were phylogenetically related to Polychaeta, Mollusca or more ancient groups, such as Cnidaria. Some toxins may have evolved from non-toxin homologs that were recruited without the reduction in molecular mass and increased specificity of other invertebrate toxins. By analyzing the phylogeny of toxin mixtures, we show that Polychaeta is uniquely positioned in the evolution of animal venoms. Indeed, the phylogenetic models of mixed or individual toxins do not follow the expected eumetazoan tree-of-life and highlight that the recruitment of gene products for a role in venom systems is complex.
27
Zhao, Hong-Yan, Yan Sun, Yu Du, Jia-Qi Li, Jin-Geng Lv, Yan-Fu Qu, Long-Hui Lin, Chi-Xian Lin, Xiang Ji, and Jian-Fang Gao. "Venom of the Annulated Sea Snake Hydrophis cyanocinctus: A Biochemically Simple but Genetically Complex Weapon." Toxins 13, no. 8 (August 6, 2021): 548. http://dx.doi.org/10.3390/toxins13080548.
Full textAbstract:
Given that the venom system in sea snakes has a role in enhancing their secondary adaption to the marine environment, it follows that elucidating the diversity and function of venom toxins will help to understand the adaptive radiation of sea snakes. We performed proteomic and de novo NGS analyses to explore the diversity of venom toxins in the annulated sea snake (Hydrophis cyanocinctus) and estimated the adaptive molecular evolution of the toxin-coding unigenes and the toxicity of the major components. We found three-finger toxins (3-FTxs), phospholipase A2 (PLA2) and cysteine-rich secretory protein (CRISP) in the venom proteome and 59 toxin-coding unigenes belonging to 24 protein families in the venom-gland transcriptome; 3-FTx and PLA2 were the most abundant families. Nearly half of the toxin-coding unigenes had undergone positive selection. The short- (i.p. 0.09 μg/g) and long-chain neurotoxin (i.p. 0.14 μg/g) presented fairly high toxicity, whereas both basic and acidic PLA2s expressed low toxicity. The toxicity of H. cyanocinctus venom was largely determined by the 3-FTxs. Our data show the venom is used by H. cyanocinctus as a biochemically simple but genetically complex weapon and venom evolution in H. cyanocinctus is presumably driven by natural selection to deal with fast-moving prey and enemies in the marine environment.
28
Sanhajariya, Suchaya, Geoffrey K. Isbister, and Stephen B. Duffull. "The Influence of the Different Disposition Characteristics of Snake Toxins on the Pharmacokinetics of Snake Venom." Toxins 12, no. 3 (March 16, 2020): 188. http://dx.doi.org/10.3390/toxins12030188.
Full textAbstract:
Snake venom is comprised of a combination of different proteins and peptides with a wide range of molecular weights and different disposition processes inherent to each compound. This causes venom to have a complex exposure profile. Our study investigates 1) how each molecular weight fraction (toxin) of venom contributes to the overall time course of the snake venom, and 2) the ability to determine toxin profiles based on the profile of the overall venom only. We undertook an in silico simulation and modelling study. Sixteen variations of venom, comprising of two to nine toxins with different molecular weights were investigated. The pharmacokinetic parameters (i.e., clearance, C L , and volume of distribution, V ) of each toxin were generated based on a log-linear relationship with molecular weight. The concentration–time data of each toxin were simulated for 100 virtual patients using MATLAB and the total concentration–time data of each toxin were modelled using NONMEM. We found that the data of sixteen mixtures were best described by either two- or three-compartment models, despite the venom being made up of more than three different toxins. This suggests that it is generally not possible to determine individual toxin profiles based on measurements of total venom concentrations only.
29
Dashevsky, Daniel, Darin Rokyta, Nathaniel Frank, Amanda Nouwens, and Bryan G. Fry. "Electric Blue: Molecular Evolution of Three-Finger Toxins in the Long-Glanded Coral Snake Species Calliophis bivirgatus." Toxins 13, no. 2 (February 8, 2021): 124. http://dx.doi.org/10.3390/toxins13020124.
Full textAbstract:
The genus Calliophis is the most basal branch of the family Elapidae and several species in it have developed highly elongated venom glands. Recent research has shown that C. bivirgatus has evolved a seemingly unique toxin (calliotoxin) that produces spastic paralysis in their prey by acting on the voltage-gated sodium (NaV) channels. We assembled a transcriptome from C. bivirgatus to investigate the molecular characteristics of these toxins and the venom as a whole. We find strong confirmation that this genus produces the classic elapid eight-cysteine three-finger toxins, that δδ-elapitoxins (toxins that resemble calliotoxin) are responsible for a substantial portion of the venom composition, and that these toxins form a distinct clade within a larger, more diverse clade of C. bivirgatus three-finger toxins. This broader clade of C. bivirgatus toxins also contains the previously named maticotoxins and is somewhat closely related to cytotoxins from other elapids. However, the toxins from this clade that have been characterized are not themselves cytotoxic. No other toxins show clear relationships to toxins of known function from other species.
30
Chong, Ho Phin, Kae Yi Tan, Nget Hong Tan, and Choo Hock Tan. "Exploring the Diversity and Novelty of Toxin Genes in Naja sumatrana, the Equatorial Spitting Cobra from Malaysia through De Novo Venom-Gland Transcriptomics." Toxins 11, no. 2 (February 11, 2019): 104. http://dx.doi.org/10.3390/toxins11020104.
Full textAbstract:
The equatorial spitting cobra, Naja sumatrana, is a distinct species of medically important venomous snakes, listed as WHO Category 1 in Southeast Asia. The diversity of its venom genes has not been comprehensively examined, although a few toxin sequences annotated to Naja sputatrix were reported previously through cloning studies. To investigate this species venom genes’ diversity, de novo venom-gland transcriptomics of N. sumatrana from West Malaysia was conducted using next-generation sequencing technology. Genes encoding toxins represented only 60 of the 55,396 transcripts, but were highly expressed, contributing to 79.22% of total gene expression (by total FPKM) in the venom-glands. The toxin transcripts belong to 21 families, and 29 transcripts were further identified as full-length. Three-finger toxins (3FTx) composed of long, short, and non-conventional groups, constituted the majority of toxin transcripts (91.11% of total toxin FPKM), followed by phospholipase A2 (PLA2, 7.42%)—which are putatively pro-inflammatory and cytotoxic. The remaining transcripts in the 19 families were expressed at extremely low levels. Presumably, these toxins were associated with ancillary functions. Our findings unveil the diverse toxin genes unique to N. sumatrana, and provide insights into the pathophysiology of N. sumatrana envenoming.
31
Odell, George V., Herlinda Clement, Lourival Possani, and Alejandro Alagón. "Spider Venom Toxins." Journal of Venomous Animals and Toxins 7, no. 2 (December 2001): 335. http://dx.doi.org/10.1590/s0104-79302001000200031.
Full text
32
Fedosov, Alexander, Paul Zaharias, and Nicolas Puillandre. "A phylogeny-aware approach reveals unexpected venom components in divergent lineages of cone snails." Proceedings of the Royal Society B: Biological Sciences 288, no. 1954 (July 7, 2021): 20211017. http://dx.doi.org/10.1098/rspb.2021.1017.
Full textAbstract:
Marine gastropods of the genus Conus are renowned for their remarkable diversity and deadly venoms. While Conus venoms are increasingly well studied for their biomedical applications, we know surprisingly little about venom composition in other lineages of Conidae. We performed comprehensive venom transcriptomic profiling for Conasprella coriolisi and Pygmaeconus traillii , first time for both respective genera. We complemented reference-based transcriptome annotation by a de novo toxin prediction guided by phylogeny, which involved transcriptomic data on two additional ‘divergent’ cone snail lineages, Profundiconus , and Californiconus . We identified toxin clusters (SSCs) shared among all or some of the four analysed genera based on the identity of the signal region—a molecular tag present in toxins. In total, 116 and 98 putative toxins represent 29 and 28 toxin gene superfamilies in Conasprella and Pygmaeconus , respectively; about quarter of these only found by semi-manual annotation of the SSCs. Two rare gene superfamilies, originally identified from fish-hunting cone snails, were detected outside Conus rather unexpectedly, so we further investigated their distribution across Conidae radiation. We demonstrate that both these, in fact, are ubiquitous in Conidae, sometimes with extremely high expression. Our findings demonstrate how a phylogeny-aware approach circumvents methodological caveats of similarity-based transcriptome annotation.
33
Chapeaurouge, Alex, Andreza Silva, Paulo Carvalho, Ryan McCleary, Cassandra Modahl, Jonas Perales, R. Kini, and Stephen Mackessy. "Proteomic Deep Mining the Venom of the Red-Headed Krait, Bungarus flaviceps." Toxins 10, no. 9 (September 13, 2018): 373. http://dx.doi.org/10.3390/toxins10090373.
Full textAbstract:
The use of -omics technologies allows for the characterization of snake venom composition at a fast rate and at high levels of detail. In the present study, we investigated the protein content of Red-headed Krait (Bungarus flaviceps) venom. This analysis revealed a high diversity of snake venom protein families, as evidenced by high-throughput mass spectrometric analysis. We found all six venom protein families previously reported in a transcriptome study of the venom gland of B. flaviceps, including phospholipases A2 (PLA2s), Kunitz-type serine proteinase inhibitors (KSPIs), three-finger toxins (3FTxs), cysteine-rich secretory proteins (CRISPs), snaclecs, and natriuretic peptides. A combined approach of automated database searches and de novo sequencing of tandem mass spectra, followed by sequence similarity searches, revealed the presence of 12 additional toxin families. De novo sequencing alone was able to identify 58 additional peptides, and this approach contributed significantly to the comprehensive description of the venom. Abundant protein families comprise 3FTxs (22.3%), KSPIs (19%), acetylcholinesterases (12.6%), PLA2s (11.9%), venom endothelial growth factors (VEGFs, 8.4%), nucleotidases (4.3%), and C-type lectin-like proteins (snaclecs, 3.3%); an additional 11 toxin families are present at significantly lower concentrations, including complement depleting factors, a family not previously detected in Bungarus venoms. The utility of a multifaceted approach toward unraveling the proteome of snake venoms, employed here, allowed detection of even minor venom components. This more in-depth knowledge of the composition of B. flaviceps venom facilitates a better understanding of snake venom molecular evolution, in turn contributing to more effective treatment of krait bites.
34
Heep, John, Marisa Skaljac, Jens Grotmann, Tobias Kessel, Maximilian Seip, Henrike Schmidtberg, and Andreas Vilcinskas. "Identification and Functional Characterization of a Novel Insecticidal Decapeptide from the Myrmicine Ant Manica rubida." Toxins 11, no. 10 (September 25, 2019): 562. http://dx.doi.org/10.3390/toxins11100562.
Full textAbstract:
Ant venoms contain many small, linear peptides, an untapped source of bioactive peptide toxins. The control of agricultural insect pests currently depends primarily on chemical insecticides, but their intensive use damages the environment and human health, and encourages the emergence of resistant pest populations. This has promoted interest in animal venoms as a source of alternative, environmentally-friendly bio-insecticides. We tested the crude venom of the predatory ant, Manica rubida, and observed severe fitness costs in the parthenogenetic pea aphid (Acyrthosiphon pisum), a common agricultural pest. Therefore, we explored the M. rubida venom peptidome and identified a novel decapeptide U-MYRTX-MANr1 (NH2-IDPKVLESLV-CONH2) using a combination of Edman degradation and de novo peptide sequencing. Although this myrmicitoxin was inactive against bacteria and fungi, it reduced aphid survival and reproduction. Furthermore, both crude venom and U-MYRTX-MANr1 reversibly paralyzed injected aphids and induced a loss of body fluids. Components of M. rubida venom may act on various biological targets including ion channels and hemolymph coagulation proteins, as previously shown for other ant venom toxins. The remarkable insecticidal activity of M. rubida venom suggests it may be a promising source of additional bio-insecticide leads.
35
Xie, Chunfang, Laura-Oana Albulescu, Mátyás A. Bittenbinder, Govert W. Somsen, Freek J. Vonk, Nicholas R. Casewell, and Jeroen Kool. "Neutralizing Effects of Small Molecule Inhibitors and Metal Chelators on Coagulopathic Viperinae Snake Venom Toxins." Biomedicines 8, no. 9 (August 20, 2020): 297. http://dx.doi.org/10.3390/biomedicines8090297.
Full textAbstract:
Animal-derived antivenoms are the only specific therapies currently available for the treatment of snake envenoming, but these products have a number of limitations associated with their efficacy, safety and affordability for use in tropical snakebite victims. Small molecule drugs and drug candidates are regarded as promising alternatives for filling the critical therapeutic gap between snake envenoming and effective treatment. In this study, by using an advanced analytical technique that combines chromatography, mass spectrometry and bioassaying, we investigated the effect of several small molecule inhibitors that target phospholipase A2 (varespladib) and snake venom metalloproteinase (marimastat, dimercaprol and DMPS) toxin families on inhibiting the activities of coagulopathic toxins found in Viperinae snake venoms. The venoms of Echis carinatus, Echis ocellatus, Daboia russelii and Bitis arietans, which are known for their potent haemotoxicities, were fractionated in high resolution onto 384-well plates using liquid chromatography followed by coagulopathic bioassaying of the obtained fractions. Bioassay activities were correlated to parallel recorded mass spectrometric and proteomics data to assign the venom toxins responsible for coagulopathic activity and assess which of these toxins could be neutralized by the inhibitors under investigation. Our results showed that the phospholipase A2-inhibitor varespladib neutralized the vast majority of anticoagulation activities found across all of the tested snake venoms. Of the snake venom metalloproteinase inhibitors, marimastat demonstrated impressive neutralization of the procoagulation activities detected in all of the tested venoms, whereas dimercaprol and DMPS could only partially neutralize these activities at the doses tested. Our results provide additional support for the concept that combinations of small molecules, particularly the combination of varespladib with marimastat, serve as a drug-repurposing opportunity to develop new broad-spectrum inhibitor-based therapies for snakebite envenoming.
36
Ahmadi, Shirin, Julius M. Knerr, Lídia Argemi, Karla C. F. Bordon, Manuela B. Pucca, Felipe A. Cerni, Eliane C. Arantes, Figen Çalışkan, and Andreas H. Laustsen. "Scorpion Venom: Detriments and Benefits." Biomedicines 8, no. 5 (May 12, 2020): 118. http://dx.doi.org/10.3390/biomedicines8050118.
Full textAbstract:
Scorpion venom may cause severe medical complications and untimely death if injected into the human body. Neurotoxins are the main components of scorpion venom that are known to be responsible for the pathological manifestations of envenoming. Besides neurotoxins, a wide range of other bioactive molecules can be found in scorpion venoms. Advances in separation, characterization, and biotechnological approaches have enabled not only the development of more effective treatments against scorpion envenomings, but have also led to the discovery of several scorpion venom peptides with interesting therapeutic properties. Thus, scorpion venom may not only be a medical threat to human health, but could prove to be a valuable source of bioactive molecules that may serve as leads for the development of new therapies against current and emerging diseases. This review presents both the detrimental and beneficial properties of scorpion venom toxins and discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.
37
Ueberheide, Beatrix M., David Fenyö, Paul F. Alewood, and Brian T. Chait. "Rapid sensitive analysis of cysteine rich peptide venom components." Proceedings of the National Academy of Sciences 106, no. 17 (April 20, 2009): 6910–15. http://dx.doi.org/10.1073/pnas.0900745106.
Full textAbstract:
Disulfide-rich peptide venoms from animals such as snakes, spiders, scorpions, and certain marine snails represent one of nature's great diversity libraries of bioactive molecules. The various species of marine cone shells have alone been estimated to produce >50,000 distinct peptide venoms. These peptides have stimulated considerable interest because of their ability to potently alter the function of specific ion channels. To date, only a small fraction of this immense resource has been characterized because of the difficulty in elucidating their primary structures, which range in size between 10 and 80 aa, include up to 5 disulfide bonds, and can contain extensive posttranslational modifications. The extraordinary complexity of crude venoms and the lack of DNA databases for many of the organisms of interest present major analytical challenges. Here, we describe a strategy that uses mass spectrometry for the elucidation of the mature peptide toxin components of crude venom samples. Key to this strategy is our use of electron transfer dissociation (ETD), a mass spectrometric fragmentation technique that can produce sequence information across the entire peptide backbone. However, because ETD only yields comprehensive sequence coverage when the charge state of the precursor peptide ion is sufficiently high and the m/z ratio is low, we combined ETD with a targeted chemical derivatization strategy to increase the charge state of cysteine-containing peptide toxins. Using this strategy, we obtained full sequences for 31 peptide toxins, using just 7% of the crude venom from the venom gland of a single cone snail (Conus textile).
38
Laustsen, Andreas H., Mikael Engmark, Christopher Clouser, Sonia Timberlake, Francois Vigneault, José María Gutiérrez, and Bruno Lomonte. "Exploration of immunoglobulin transcriptomes from mice immunized with three-finger toxins and phospholipases A2from the Central American coral snake,Micrurus nigrocinctus." PeerJ 5 (January 24, 2017): e2924. http://dx.doi.org/10.7717/peerj.2924.
Full textAbstract:
Snakebite envenomings represent a neglected public health issue in many parts of the rural tropical world. Animal-derived antivenoms have existed for more than a hundred years and are effective in neutralizing snake venom toxins when timely administered. However, the low immunogenicity of many small but potent snake venom toxins represents a challenge for obtaining a balanced immune response against the medically relevant components of the venom. Here, we employ high-throughput sequencing of the immunoglobulin (Ig) transcriptome of mice immunized with a three-finger toxin and a phospholipase A2from the venom of the Central American coral snake,Micrurus nigrocinctus.Although exploratory in nature, our indicate results showed that only low frequencies of mRNA encoding IgG isotypes, the most relevant isotype for therapeutic purposes, were present in splenocytes of five mice immunized with 6 doses of the two types of toxins over 90 days. Furthermore, analysis of Ig heavy chain transcripts showed that no particular combination of variable (V) and joining (J) gene segments had been selected in the immunization process, as would be expected after a strong humoral immune response to a single antigen. Combined with the titration of toxin-specific antibodies in the sera of immunized mice, these data support the low immunogenicity of three-finger toxins and phospholipases A2found inM. nigrocinctusvenoms, and highlight the need for future studies analyzing the complexity of antibody responses to toxins at the molecular level.
39
Xie, Chunfang, Julien Slagboom, Laura-Oana Albulescu, Ben Bruyneel, Kristina B. M. Still, Freek J. Vonk, Govert W. Somsen, Nicholas R. Casewell, and Jeroen Kool. "Antivenom Neutralization of Coagulopathic Snake Venom Toxins Assessed by Bioactivity Profiling Using Nanofractionation Analytics." Toxins 12, no. 1 (January 16, 2020): 53. http://dx.doi.org/10.3390/toxins12010053.
Full textAbstract:
Venomous snakebite is one of the world’s most lethal neglected tropical diseases. Animal-derived antivenoms are the only standardized specific therapies currently available for treating snakebite envenoming, but due to venom variation, often this treatment is not effective in counteracting all clinical symptoms caused by the multitude of injected toxins. In this study, the coagulopathic toxicities of venoms from the medically relevant snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus and Echis ocellatus were assessed. The venoms were separated by liquid chromatography (LC) followed by nanofractionation and parallel mass spectrometry (MS). A recently developed high-throughput coagulation assay was employed to assess both the pro- and anticoagulant activity of separated venom toxins. The neutralization capacity of antivenoms on separated venom components was assessed and the coagulopathic venom peptides and enzymes that were either neutralized or remained active in the presence of antivenom were identified by correlating bioassay results with the MS data and with off-line generated proteomics data. The results showed that most snake venoms analyzed contained both procoagulants and anticoagulants. Most anticoagulants were identified as phospholipases A2s (PLA2s) and most procoagulants correlated with snake venom metalloproteinases (SVMPs) and serine proteases (SVSPs). This information can be used to better understand antivenom neutralization and can aid in the development of next-generation antivenom treatments.
40
Suryamohan, Kushal, Sajesh P. Krishnankutty, Joseph Guillory, Matthew Jevit, Markus S. Schröder, Meng Wu, Boney Kuriakose, et al. "The Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins." Nature Genetics 52, no. 1 (January 2020): 106–17. http://dx.doi.org/10.1038/s41588-019-0559-8.
Full textAbstract:
AbstractSnakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of effective humanized recombinant antivenom. We report a de novo near-chromosomal genome assembly of Naja naja, the Indian cobra, a highly venomous, medically important snake. Our assembly has a scaffold N50 of 223.35 Mb, with 19 scaffolds containing 95% of the genome. Of the 23,248 predicted protein-coding genes, 12,346 venom-gland-expressed genes constitute the ‘venom-ome’ and this included 139 genes from 33 toxin families. Among the 139 toxin genes were 19 ‘venom-ome-specific toxins’ (VSTs) that showed venom-gland-specific expression, and these probably encode the minimal core venom effector proteins. Synthetic venom reconstituted through recombinant VST expression will aid in the rapid development of safe and effective synthetic antivenom. Additionally, our genome could serve as a reference for snake genomes, support evolutionary studies and enable venom-driven drug discovery.
41
Bastida, Jeny, Alejandro Crampet, Melitta Meneghel, and Victor Morais. "Preliminary Biochemical and Venomic Characterization of the Venom of Phalotris lemniscatus (Serpentes, Colubridae)." Current Topics in Medicinal Chemistry 19, no. 22 (October 24, 2019): 1981–89. http://dx.doi.org/10.2174/1568026619666190802143252.
Full textAbstract:
Background: For many decades, research on snake venom toxinology focused mainly on the venoms of Viperidae and Elapidae species, which were traditionally the only ones considered as venomous. However, much less interest has been given to the venom produced by opisthoglyphous colubrid snakes, since they were typically considered of no clinical relevance. Objective: The aim of this work is to perform a preliminary biochemical and venomic characterization of the venom of the colubrid snake Phalotris lemniscatus, a species that has been responsible for two relevant cases of envenomation in Uruguay. Methods: We extracted venom from collected specimens and performed different biochemical and proteomic assays to understand its toxin composition. Results: We found that the venom of P. lemniscatus is composed of protein families typically present in snake venoms, such as metallo and serine preoteases, L-amino acid oxidases, phospholipases A2s, Ctype lectines-like, Kunitz-type proteins and three-finger toxins. Activity assays demonstrated a highly active gelatinolytic component as well as a potent capability to induce blood coagulation. Conclusion: The results indicate that the venom of P. lemniscatus contains hemotoxic activities and components that resemble those found in Viperidae (Bothrops) snakes and that can induce a clinically relevant accident. Further studies are needed to better understand the venom composition of this colubrid snake and its most active compounds.
42
Rádis-Baptista, Gandhi. "Cell-Penetrating Peptides Derived from Animal Venoms and Toxins." Toxins 13, no. 2 (February 15, 2021): 147. http://dx.doi.org/10.3390/toxins13020147.
Full textAbstract:
Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, organelles (e.g., the nucleus and mitochondria) and other subcellular compartments. CPPs are either of natural origin or de novo designed and synthesized from segments and patches of larger proteins or designed by algorithms. With such intrinsic properties, along with membrane permeation, translocation and cellular uptake properties, CPPs can intracellularly convey diverse substances and nanomaterials, such as hydrophilic organic compounds and drugs, macromolecules (nucleic acids and proteins), nanoparticles (nanocrystals and polyplexes), metals and radionuclides, which can be covalently attached via CPP N- and C-terminals or through preparation of CPP complexes. A cumulative number of studies on animal toxins, primarily isolated from the venom of arthropods and snakes, have revealed the cell-penetrating activities of venom peptides and toxins, which can be harnessed for application in biomedicine and pharmaceutical biotechnology. In this review, I aimed to collate examples of peptides from animal venoms and toxic secretions that possess the ability to penetrate diverse types of cells. These venom CPPs have been chemically or structurally modified to enhance cell selectivity, bioavailability and a range of target applications. Herein, examples are listed and discussed, including cysteine-stabilized and linear, α-helical peptides, with cationic and amphipathic character, from the venom of insects (e.g., melittin, anoplin, mastoparans), arachnids (latarcin, lycosin, chlorotoxin, maurocalcine/imperatoxin homologs and wasabi receptor toxin), fish (pardaxins), amphibian (bombesin) and snakes (crotamine and cathelicidins).
43
Neri-Castro, Edgar, Melisa Bénard-Valle, Dayanira Paniagua, Leslie V. Boyer, Lourival D. Possani, Fernando López-Casillas, Alejandro Olvera, Camilo Romero, Fernando Zamudio, and Alejandro Alagón. "Neotropical Rattlesnake (Crotalus simus) Venom Pharmacokinetics in Lymph and Blood Using an Ovine Model." Toxins 12, no. 7 (July 17, 2020): 455. http://dx.doi.org/10.3390/toxins12070455.
Full textAbstract:
The most abundant protein families in viper venoms are Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs) and Phospholipases (PLA2s). These are primarily responsible for the pathophysiology caused by the bite of pit-vipers; however, there are few studies that analyze the pharmacokinetics (PK) of whole venom (WV) and its protein families. We studied the pathophysiology, PK profile and differential absorption of representative toxins from venom of Neotropical Rattlesnake (Crotalus simus) in a large animal model (ovine). Toxins studied included crotoxin (the main lethal component), which causes moderate to severe neurotoxicity; SVSPs, which deplete fibrinogen; and SVMPs, which cause local tissue damage and local and systemic hemorrhage. We found that Whole Venom (WV) was highly bioavailable (86%) 60 h following intramuscular (IM) injection, and extrapolation suggests that bioavailability may be as high as 92%. PK profiles of individual toxins were consistent with their physicochemical properties and expected clinical effects. Lymph cannulated animals absorbed 1.9% of WV through lymph during the first 12 h. Crotoxin was minimally detectable in serum after intravenous (IV) injection; however, following IM injection it was detected in lymph but not in blood. This suggests that crotoxin is quickly released from the blood toward its tissue targets.
44
Harris, Richard J., Christina N. Zdenek, David Harrich, Nathaniel Frank, and Bryan G. Fry. "An Appetite for Destruction: Detecting Prey-Selective Binding of α-Neurotoxins in the Venom of Afro-Asian Elapids." Toxins 12, no. 3 (March 23, 2020): 205. http://dx.doi.org/10.3390/toxins12030205.
Full textAbstract:
Prey-selective venoms and toxins have been documented across only a few species of snakes. The lack of research in this area has been due to the absence of suitably flexible testing platforms. In order to test more species for prey specificity of their venom, we used an innovative taxonomically flexible, high-throughput biolayer interferometry approach to ascertain the relative binding of 29 α-neurotoxic venoms from African and Asian elapid representatives (26 Naja spp., Aspidelaps scutatus, Elapsoidea boulengeri, and four locales of Ophiophagus hannah) to the alpha-1 nicotinic acetylcholine receptor orthosteric (active) site for amphibian, lizard, snake, bird, and rodent targets. Our results detected prey-selective, intraspecific, and geographical differences of α-neurotoxic binding. The results also suggest that crude venom that shows prey selectivity is likely driven by the proportions of prey-specific α-neurotoxins with differential selectivity within the crude venom. Our results also suggest that since the α-neurotoxic prey targeting does not always account for the full dietary breadth of a species, other toxin classes with a different pathophysiological function likely play an equally important role in prey immobilisation of the crude venom depending on the prey type envenomated. The use of this innovative and taxonomically flexible diverse assay in functional venom testing can be key in attempting to understanding the evolution and ecology of α-neurotoxic snake venoms, as well as opening up biochemical and pharmacological avenues to explore other venom effects.
45
Sachkova, Maria Y., Shir A. Singer, Jason Macrander, Adam M. Reitzel, Steve Peigneur, Jan Tytgat, and Yehu Moran. "The Birth and Death of Toxins with Distinct Functions: A Case Study in the Sea Anemone Nematostella." Molecular Biology and Evolution 36, no. 9 (May 27, 2019): 2001–12. http://dx.doi.org/10.1093/molbev/msz132.
Full textAbstract:
Abstract The cnidarian Nematostella vectensis has become an established lab model, providing unique opportunities for venom evolution research. The Nematostella venom system is multimodal: involving both nematocytes and ectodermal gland cells, which produce a toxin mixture whose composition changes throughout the life cycle. Additionally, their modes of interaction with predators and prey vary between eggs, larvae, and adults, which is likely shaped by the dynamics of the venom system. Nv1 is a major component of adult venom, with activity against arthropods (through specific inhibition of sodium channel inactivation) and fish. Nv1 is encoded by a cluster of at least 12 nearly identical genes that were proposed to be undergoing concerted evolution. Surprisingly, we found that Nematostella venom includes several Nv1 paralogs escaping a pattern of general concerted evolution, despite belonging to the Nv1-like family. Here, we show two of these new toxins, Nv4 and Nv5, are lethal for zebrafish larvae but harmless to arthropods, unlike Nv1. Furthermore, unlike Nv1, the newly identified toxins are expressed in early life stages. Using transgenesis and immunostaining, we demonstrate that Nv4 and Nv5 are localized to ectodermal gland cells in larvae. The evolution of Nv4 and Nv5 can be described either as neofunctionalization or as subfunctionalization. Additionally, the Nv1-like family includes several pseudogenes being an example of nonfunctionalization and venom evolution through birth-and-death mechanism. Our findings reveal the evolutionary history for a toxin radiation and point toward the ecological function of the novel toxins constituting a complex cnidarian venom.
46
Rügen, Nicolai, Timothy P. Jenkins, Natalie Wielsch, Heiko Vogel, Benjamin-Florian Hempel, Roderich D. Süssmuth, Stuart Ainsworth, Alejandro Cabezas-Cruz, Andreas Vilcinskas, and Miray Tonk. "Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus." Biomedicines 9, no. 7 (July 14, 2021): 819. http://dx.doi.org/10.3390/biomedicines9070819.
Full textAbstract:
Assassin bug venoms are potent and exert diverse biological functions, making them potential biomedical goldmines. Besides feeding functions on arthropods, assassin bugs also use their venom for defense purposes causing localized and systemic reactions in vertebrates. However, assassin bug venoms remain poorly characterized. We collected the venom from the assassin bug Rhynocoris iracundus and investigated its composition and bioactivity in vitro and in vivo. It caused lysis of murine neuroblastoma, hepatoma cells, and healthy murine myoblasts. We demonstrated, for the first time, that assassin bug venom induces neurolysis and suggest that it counteracts paralysis locally via the destruction of neural networks, contributing to tissue digestion. Furthermore, the venom caused paralysis and melanization of Galleria mellonella larvae and pupae, whilst also possessing specific antibacterial activity against Escherichia coli, but not Listeria grayi and Pseudomonas aeruginosa. A combinatorial proteo-transcriptomic approach was performed to identify potential toxins responsible for the observed effects. We identified neurotoxic Ptu1, an inhibitory cystin knot (ICK) toxin homologous to ω-conotoxins from cone snails, cytolytic redulysins homologous to trialysins from hematophagous kissing bugs, and pore-forming hemolysins. Additionally, chitinases and kininogens were found and may be responsible for insecticidal and cytolytic activities. We demonstrate the multifunctionality and complexity of assassin bug venom, which renders its molecular components interesting for potential biomedical applications.
47
dos Santos, Ana P., Tamara G. de Araújo, and Gandhi Rádis-Baptista. "Nanoparticles Functionalized with Venom-Derived Peptides and Toxins for Pharmaceutical Applications." Current Pharmaceutical Biotechnology 21, no. 2 (February 12, 2020): 97–109. http://dx.doi.org/10.2174/1389201020666190621104624.
Full textAbstract:
Venom-derived peptides display diverse biological and pharmacological activities, making them useful in drug discovery platforms and for a wide range of applications in medicine and pharmaceutical biotechnology. Due to their target specificities, venom peptides have the potential to be developed into biopharmaceuticals to treat various health conditions such as diabetes mellitus, hypertension, and chronic pain. Despite the high potential for drug development, several limitations preclude the direct use of peptides as therapeutics and hamper the process of converting venom peptides into pharmaceuticals. These limitations include, for instance, chemical instability, poor oral absorption, short halflife, and off-target cytotoxicity. One strategy to overcome these disadvantages relies on the formulation of bioactive peptides with nanocarriers. A range of biocompatible materials are now available that can serve as nanocarriers and can improve the bioavailability of therapeutic and venom-derived peptides for clinical and diagnostic application. Examples of isolated venom peptides and crude animal venoms that have been encapsulated and formulated with different types of nanomaterials with promising results are increasingly reported. Based on the current data, a wealth of information can be collected regarding the utilization of nanocarriers to encapsulate venom peptides and render them bioavailable for pharmaceutical use. Overall, nanomaterials arise as essential components in the preparation of biopharmaceuticals that are based on biological and pharmacological active venom-derived peptides.
48
Calabria, Paula, Lhiri Shimokawa-Falcão, Monica Colombini, Ana Moura-da-Silva, Katia Barbaro, Eliana Faquim-Mauro, and Geraldo Magalhaes. "Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against Loxosceles Spider Venom." Toxins 11, no. 2 (February 12, 2019): 108. http://dx.doi.org/10.3390/toxins11020108.
Full textAbstract:
Human accidents with spiders of the genus Loxosceles are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to be the most effective treatment. However, for antivenom production, the extraction of the venom used in the immunization process is laborious and the yield is very low. Thus, many groups have been exploring the use of recombinant Loxosceles toxins, particularly phospholipases D (PLDs), to produce the antivenom. Nonetheless, some important venom activities are not neutralized by anti-PLD antibodies. Astacin-like metalloproteases (ALMPs) are the second most expressed toxin acting on the extracellular matrix, indicating the importance of its inclusion in the antigen’s formulation to provide a better antivenom. Here we show the construction of a hybrid recombinant immunogen, called LgRec1ALP1, composed of hydrophilic regions of the PLD and the ALMP toxins from Loxosceles gaucho. Although the LgRec1ALP1 was expressed as inclusion bodies, it resulted in good yields and it was effective to produce neutralizing antibodies in mice. The antiserum neutralized fibrinogenolytic, platelet aggregation and dermonecrotic activities elicited by L. gaucho, L. laeta, and L. intermedia venoms, indicating that the hybrid recombinant antigen may be a valuable source for the production of protective antibodies against Loxosceles ssp. venoms. In addition, the hybrid recombinant toxin approach may enrich and expand the alternative antigens for antisera production for other venoms.
49
Martin-Eauclaire, Marie-France, Sonia Adi-Bessalem, Djelila Hammoudi-Triki, Fatima Laraba-Djebari, and Pierre E. Bougis. "Serotherapy against Voltage-Gated Sodium Channel-Targeting αToxins from Androctonus Scorpion Venom." Toxins 11, no. 2 (January 23, 2019): 63. http://dx.doi.org/10.3390/toxins11020063.
Full textAbstract:
Because of their venom lethality towards mammals, scorpions of the Androctonus genus are considered a critical threat to human health in North Africa. Several decades of exploration have led to a comprehensive inventory of their venom components at chemical, pharmacological, and immunological levels. Typically, these venoms contain selective and high affinity ligands for the voltage-gated sodium (Nav) and potassium (Kv) channels that dictate cellular excitability. In the well-studied Androctonus australis and Androctonus mauretanicus venoms, almost all the lethality in mammals is due to the so-called α-toxins. These peptides commonly delay the fast inactivation process of Nav channels, which leads to increased sodium entry and a subsequent cell membrane depolarization. Markedly, their neutralization by specific antisera has been shown to completely inhibit the venom’s lethal activity, because they are not only the most abundant venom peptide but also the most fatal. However, the structural and antigenic polymorphisms in the α-toxin family pose challenges to the design of efficient serotherapies. In this review, we discuss past and present accomplishments to improve serotherapy against Androctonus scorpion stings.
50
Wait, Laura C., Andrew A. Walker, and Glenn F. King. "Crouching Tiger, Hidden Protein: Searching for Insecticidal Toxins in Venom of the Red Tiger Assassin Bug (Havinthus rufovarius)." Toxins 13, no. 1 (December 22, 2020): 3. http://dx.doi.org/10.3390/toxins13010003.
Full textAbstract:
Assassin bugs are venomous insects that prey on other arthropods. Their venom has lethal, paralytic, and liquifying effects when injected into prey, but the toxins responsible for these effects are unknown. To identify bioactive assassin bug toxins, venom was harvested from the red tiger assassin bug (Havinthus rufovarius), an Australian species whose venom has not previously been characterised. The venom was fractionated using reversed-phase high-performance liquid chromatography, and four fractions were found to cause paralysis and death when injected into sheep blowflies (Lucilia cuprina). The amino acid sequences of the major proteins in two of these fractions were elucidated by comparing liquid chromatography/tandem mass spectrometry data with a translated venom-gland transcriptome. The most abundant components were identified as a solitary 12.8 kDa CUB (complement C1r/C1s, Uegf, Bmp1) domain protein and a 9.5 kDa cystatin. CUB domains are present in multidomain proteins with diverse functions, including insect proteases. Although solitary CUB domain proteins have been reported to exist in other heteropteran venoms, such as that of the bee killer assassin bug Pristhesancus plagipennis, their function is unknown, and they have not previously been reported as lethal or paralysis-inducing. Cystatins occur in the venoms of spiders and snakes, but again with an unknown function. Reduction and alkylation experiments revealed that the H. rufovarius venom cystatin featured five cysteine residues, one of which featured a free sulfhydryl group. These data suggest that solitary CUB domain proteins and/or cystatins may contribute to the insecticidal activity of assassin bug venom.