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Animal poisons and venoms are comprised of different classes of molecules displaying wide-ranging pharmacological activities. This review aims to provide an in-depth view of toxin-based compounds from terrestrial and marine organisms used as diagnostic tools, experimental molecules to validate postulated therapeutic targets, drug libraries, prototy...
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Context 1
... the 11 approved toxin-based molecules marketed, one molecule (ziconotide) is obtained from cone snails, two from lizards (exenatide and lixisenatide), two from leeches (bivalirudin and desirudin), and six from snakes (captopril, enalapril, tirofiban, eptifibatide, batroxobin, and cobratide). Batroxobin and cobratide are native compounds purified from snake venoms, desirudin is a recombinant molecule, and the other drugs (bivalirudin, captopril, enalapril, eptifibatide, exenatide, tirofiban, and ziconotide) are synthetic molecules ( Table 1). ...Context 2
... the susceptibility to blood proteases, as well as their immunogenicity, which are directly linked to biopharmaceutical degradation in vivo, are also important factors to be considered. Due to the relatively large size and other specific physicochemical properties, parenteral administration is currently the most used delivery route for approved venom-based drugs ( Table 1) (Ibraheem et al., 2014;Duskey et al., 2017). ...Citations
... TREATMENT TO ENVRNOM: (26,33) As envenoming is a major issue worldwide, it is very necessary to develop a therapy, process or any pharmaceutical formulation for the venom to be neutralized when injected in a healthy animal. Multiple formulations are available in market to treat envenoming. ...
Venom is a biochemical mixture of proteins that have both positive and negative aspects. Snake venom is used in the production of a number of pharmaceutical formulations. It plays a vital role in medical field including a large number of drug formulation and also production of genetically engineered venom provide an effective result in a shorter period of time. Once snake bites a person, the person may die immediately due to blockage of nervous system or may take some time to envenom including renal dysfunction, neural blockage, toxicity and hemorrhagic diathesis. On the other hand, venom is considered as a blessing that treat many diseases like blood sugar control, cancer therapy and used in preparation of therapeutics for smallpox or wound healing. Venom is available in various forms at different price depending on the type of venom to be taken and availability of rare to rarer reptile to produce the venom. In fact, however in most of the cases, the venoms of fatal snakes are found to be clinically and diagnostically potential and active.
... Animal venoms provide a remarkably abundant and diverse source of unique proteins and peptides, many with medically-relevant activities (Saez et al., 2010;Herzig et al., 2020;Bordon et al., 2020). Venomous animals have recruited many different toxins, which are used to capture prey, to facilitate feeding, for intraspecific competition and to deter predators (Schendel et al., 2019;Lüddecke et al., 2022). ...
Spider-derived peptides with insecticidal, antimicrobial and/or cytolytic activities, also known as spider venom antimicrobial peptides (AMPs), can be found in the venoms of RTA-clade spiders. They show translational potential as therapeutic leads. A set of 52 AMPs has been described in the Chinese wolf spider (Lycosa shansia), and many have been shown to exhibit antibacterial effects. Here we explored the potential to enhance their antimicrobial activity using bioengineering. We generated a panel of artificial derivatives of an A-family peptide and screened their activity against selected microbial pathogens, vertebrate cells and insects. In several cases, we increased the antimicrobial activity of the derivatives while retaining the low cytotoxicity of the parental molecule. Furthermore, we injected the peptides into adult Drosophila suzukii and found no evidence of insecticidal effects, confirming the low levels of toxicity. Our data therefore suggest that spider venom linear peptides naturally defend the venom gland against microbial colonization and can be modified into more potent antimicrobial agents that could help to battle infectious diseases in the future.
... This was demonstrated by studies on the venom composition of several other groups previously neglected in venom research [13][14][15][16][17]. Toxins from animal venoms are known to target a plethora of physiological processes and hence are suitable candidates for new lead compounds [18,19]. So far, at least eleven approved drugs have been developed based on compounds discovered in animal venoms [20]. In addition, several compounds with promising activities against diseases like epilepsy, chronic pain, autoimmune diseases, stroke, and diabetes [21][22][23][24][25] emphasize the potential of animal venoms in this regard. ...
The larvae of some lampyrid beetles are highly specialized predators of snails. They have been observed to climb on the shells of their prey and use this exposed position to bite and inject secretions potentially originating from the midgut. Besides serving the purpose of extra-oral digestion (EOD), injected compounds also seem to have a paralyzing effect. Up to now, the toxins causing this paralyzing activity have not been identified. In the current study, we provide a first compositional analysis of the midgut secretion from lampyrid larvae, with a focus on identifying putative neurotoxins causing the observed paralyzing effect. For this purpose, we utilized a combined proteo-transcriptomic approach to characterize the compounds present in the midgut secretion of larval stages of Lampyris noctiluca. In terms of the absolute numbers of identified compounds, the midgut secretion is dominated by hydrolyzing enzymes comprising peptidases, carboxylesterases, and glycosidases. However, when considering expression levels, a few rather short cysteine-rich peptides exceed all other compounds. Some of these compounds show moderate similarity to putative neurotoxins identified in the venom of other arthropods and could be responsible for paralyzing effects. In addition to these potential toxins, we provide a list of peptides typical of the midgut secretion of L. noctiluca, supplemented by the corresponding precursor sequences.
... Even though the concept became popularised by nutraceutical research (refer to Kussmann et al., 2023, for a recent review), 'natural bioactive' is far from being exhausted by food additive research and applications. In fact, compounds that interfere with specific molecular and downstream physiological processes hold great value as pharmaceuticals, for instance, depending on their specificity, potency and safety (Lindequist, 2016;Bordon et al., 2020). Many marine organisms secrete natural antibiotics, anti-foulants and defensive repellents, without neglecting venomous and poisonous animals that inject (in the first case) cocktails of neurotoxins with potential value as painkillers into their target recipients, just to mention few examples (Shen et al., 2000;Rodrigo and Costa, 2019;Turner et al., 2020;Guryanova et al., 2023). ...
The vast biological and biochemical diversity of the global ocean is the driver behind marine bioprospecting for novel bioproducts. As Marine Biotechnology is gaining momentum as one of the main pillars of the ‘Brue Growth’ revolution, the ability to screen for novel compounds of interest in species with little or no genomic resources is paramount. With this respect, proteins, which are easily metabolised, can be synthetised using convenient DNA recombinant methods and can easily be modified to better meet the needs of human society, making them prized targets. Evidently, proteins that hold natural bioactivity and specificity such as toxins and other venom components, have long captured the focus of biotechnologists, leading to the merger between environmental omics and toxinology termed as ‘venomics’. Indeed, bioactive proteins such as conopeptides, conotoxins, turripeptides and others are long deemed important subjects of research. Even though current mainstream paradigms set the focus on secondary metabolites from marine organisms, transcriptomics and proteomics approaches and their combination are rising strategies for screening for thousands of proteins and peptides in non-conventional biological models, emphasising, but not limited to, marine invertebrate animals due to their abundance, biodiversity and uncanny biochemical strategies to cope with selective pressure in literally every known marine habitat. Untargeted approaches, such as RNA-Seq – based transcriptomics and tandem mass spectrometry – based proteomics, can circumvent limitations related with absent or reduced genomic annotation. The present review will outline the main contributions of ‘omics’ and computational approaches for bioprospecting for proteinaceous marine bioactives. Despite the relatively low number of ‘omics’ studies with the main purpose of discover novel compounds, there is already important literature showcasing pipelines and approaches for revolutionising the exploration of the ocean.
... Animal venom is a source of proteins and cationic peptides, with possibilities for pharmacological applications that can serve as the basis for new drugs. 7 Studies of venoms from scorpions in the Amazon region are scarce. 8 However, they demonstrate therapeutic potential against various microorganisms, such as fungi, bacteria and viruses. ...
Scorpion venoms contain different classes of molecules with possible pharmacological activities, making them sources of bioactive molecules for the development of new drugs against infections caused by pathogens, such as malaria, a disease caused by protozoa of the genus Plasmodium. Malaria faces challenges in its control due to pathogen resistance to available antimalarials.
In this study, we evaluated the venom activity of the Amazonian scorpions and against FRC3, the analysis was performed by flow cytometry.
At the analyzed concentrations, we found that the crude venom of had an average inhibition of 87% at the concentration of 100 µg/mL, above that obtained with the drug (quinine), which had mean inhibition of 84% against FCR3. Regarding the venom of , lower activity was observed in comparison with the inhibition potential of the venom and the standard drug, venom showed low toxicity against the human fibroblast MRC5.
Because peptides and toxins from scorpion venom are related to biological functions, they can be used in the design of new therapeutic agents, with venom being a possible source of molecules for the development of antimalarial drugs.
... Each venom is composed of numerous compounds that possess a variety of bioactivities (i.e., proteolytic, hemotoxic, neurotoxic, or cytotoxic activity), and collectively serve a variety of biological functions for the host animal, including predation, defense from predators, and competitor deterrence [1,2]. Although several individual venom compounds have been developed into therapeutic drugs, including blood pressure regulators, blood thinners (anticoagulants), and pain relievers associated with specific ion channel blockers, none to date have originated from stingray venom (SRV) [3][4][5][6]. ...
The venom-containing barb attached to their ‘whip-like’ tail provides stingrays a defensive mechanism for evading predators such as sharks. From human encounters, dermal stingray envenomation is characterized by intense pain often followed by tissue necrosis occurring over several days to weeks. The bioactive components in stingray venoms (SRVs) and their molecular targets and mechanisms that mediate these complex responses are not well understood. Given the utility of venom-derived proteins from other venomous species for biomedical and pharmaceutical applications, we set out to characterize the bioactivity of SRV extracts from three local species that belong to the Dasyatoidea ‘whiptail’ superfamily. Multiple cell-based assays were used to quantify and compare the in vitro effects of these SRVs on different cell lines. All three SRVs demonstrated concentration-dependent growth-inhibitory effects on three different human cell lines tested. In contrast, a mouse fibrosarcoma cell line was markedly resistant to all three SRVs, indicating the molecular target(s) for mediating the SRV effects are not expressed on these cells. The multifunctional SRV responses were characterized by an acute disruption of cell adhesion leading to apoptosis. These findings aim to guide future investigations of individual SRV proteins and their molecular targets for potential use in biomedical applications.
... Among all marine invertebrates, cnidarians are one of the taxonomic groups for which a wide variety of proteinaceous toxins, and other venom bioactives have already been characterised and even proposed for potential biotechnological applications, despite the lack of consumer end products (refer to the recent reviews by Bordon et al. [33] and Amreen Nisa et al. [34]). The findings summarised in Figure 9 highlight some of the biological processes that may be modulated by components of the anemone's venom, from haemolysis and inflammation to apoptosis and response to bacteria (see also the full list of matched proteins and respective accessions in Supplementary Materials). ...
Simple Summary
The unsurmountable diversity of marine life is an invaluable reservoir of natural compounds for drug discovery, amongst which toxins and other bioactive molecules in venoms and poisons are prized targets. Cnidarians are some of the best-studied marine venomous animals, yet most venom components remain unidentified. This study focuses on the sea anemone Actinia equina from Portuguese intertidal zones, comparing two common morphotypes, “green” and “red”, ultimately aiming to explore its potential as a source of bioactive compounds. We provide detailed examinations of A. equina’s anatomy and microanatomy, a proteomics analysis to identify proteinaceous toxins in its tentacles and toxicity testing on zebrafish embryos. The study confirms the presence of venom-injecting cells (nematocysts) in the tentacles but finds no differences between green and red varieties. Various toxins, including neurotoxins and pore-forming proteins, were discovered. Both green and red extracts exhibit toxicity to zebrafish embryos, with green anemones appearing more potent. Overall, this study unveils proteinaceous toxins in A. equina and demonstrates that different varieties harbour distinct bioactive compounds. Besides ecological considerations, these findings bring further promise to bioprospecting A. equina for novel toxins with potential biotechnological and biomedical interest.
Abstract
The current study investigates the venom-delivery system of green and red morphotypes of the sea anemone Actinia equina to disclose its potential as a source of bioactive compounds. We compared the two morphotypes using electron and optical microscopy, proteomics, and toxicity assessment on zebrafish embryos. Specialized venom-injecting cells (nematocysts) are equally distributed and found in the tentacles of both varieties. Proteomics revealed proteins of interest in both red and green Actinia, yielding the three most abundant Gene Ontology (GO) terms related to the biological processes “proteolysis”, “hemolysis in another organism” and “lipid catabolic process”. Neurotoxins and cytolytic toxins similar to known cnidarian toxins like PsTX-60A and AvTX-60A, for instance, were identified in both types. Extracts from green and red anemones were toxic to zebrafish embryos, with green anemone venom appearing to be more potent. The findings highlight the presence of proteinaceous toxins in A. equina and the potential for different varieties to possess distinct bioactive compounds. Notably, pore-forming toxins are suggested for molecular probes and immunotoxins, making them valuable assets for potential biotechnological and biomedical purposes.
... If fibre degradation is partial, inflammation is sustained by type I macrophages that suppress myoblast formation [20,21]. Experimental regeneration can be induced using local anaesthetics or naturally occurring toxins like snake venoms [22,23]. Bupivacaine is probably one of the most often used local anaesthetics for this purpose [24,25], while notexin from the Australian tiger snake [26] is a 2 of 14 frequently applied venom. ...
The low efficiency of in vivo transfection of a few fibres revealed a novel tissue network that temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibres began to grow after complete fibre degradation, synchronous inflammation, myoblast and myotube formation. Neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) was first detected in this system. The neonatal, fast and slow SERCA isoforms displayed consequent changes with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that expression of the slow myosin heavy chain and the slow muscle type SERCA2a are differentially regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SERCA1b shRNA stimulated fibre size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished by co-transfection of Cain or with perimuscular injection of IL4 antibody. This revealed a novel signalling network resembling scale-free networks which, starting from transfected fibre myonuclei as “hubs”, can amplify growth stimulation uniformly in the entire regenerating muscle.
... One of the main sources of AMPs in nature are animal toxins. In fact, numerous compounds with antimicrobial activity have been isolated from the venom of spiders, scorpions, snakes, frogs, bees, wasps, ants and other animals, highlighting this biological matrix as a potential source for the search for new antimicrobials against MRSA [15,16]. Herein, our group has isolated a peptide containing 25 amino acid residues (H-IWLTALKFLGKNLGKHLAKQQLAKL-NH 2 ) from the venom of the Brazilian spider Lycosa erythrognatha, popularly known as the "aranha-lobo", "aranha-de-jardim", or "tarantula", which has demonstrated good antimicrobial activity. ...
... Despite the numerous advantages that the studied compound presents over vancomycin, alpha-helical AMPs such as LyeTx I mn∆K usually show disadvantages that may limit their clinical use. These agents have recognized toxicity, especially renal and cerebral, are quickly eliminated by glomerular filtration due to low binding to plasma proteins, have a large volume of distribution, are very sensitive to degradation by serum peptidases, and are compounds that have a high production cost [15,29,40]. Therefore, in order to avoid several of these limitations that could make the therapeutic use of LyeTx I mn∆K unfeasible, we chose to develop a topical formulation containing the compound. ...
... Corroborating these findings, previous studies have shown that the LyeTx I mn∆K peptide has reduced cytotoxicity activity against eukaryotic cells. The concentration required to kill 50% (CC 50 ) of Lund human mesencephalic cells (LUHMES; CC 50 15.02 µM) [18] and African green monkey (Chlorocebus aethiops) kidney epithelium cells (Vero; CC 50 55.31 ...
The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8–16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.
... Animal venoms provide a remarkably abundant and diverse source of unique proteins and peptides, many with medically-relevant activities [1][2][3].Venomous animals have recruited many different toxins, which are used to capture prey, to facilitate feeding, for intraspecific competition and to deter predators [4,5]. A particularly rich source of biomolecules is found in spiders which have the potential to yield ~10 million unique toxins. ...
Peptides with insecticidal, antimicrobial and/or cytolytic activities, also known as spider venom antimicrobial peptides (AMPs), can be found in the venoms of RTA-clade spiders. They show translational potential as therapeutic leads. A set of 52 AMPs has been described in the Chinese wolf spider (Lycosa shansia), and many have been shown to exhibit antibacterial effects. Here we explored the potential to enhance their antimicrobial activity using bioengineering. We generated a panel of artificial derivatives of an A-family peptide and screened their activity against selected microbial pathogens, vertebrate cells and insects. In several cases, we increased the antimicrobial activity of the derivatives while retaining the low cytotoxicity of the parental molecule. Furthermore, we injected the peptides into adult Drosophila suzukii and found no evidence of insecticidal effects, confirming the low levels of toxicity. Our data therefore suggest that spider venom linear peptides can be modified into more potent antimicrobial agents that could help to battle infectious diseases in the future.
