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Envenomation by an aquatic animal can produce distressing and occasionally life-threatening signs and symptoms. Common vectors of exposure in the US are cnidaria and venomous fish. Prompt recognition and treatment may help manage distressing symptoms, limit subsequent tissue destruction, and minimize the risk of more serious complications. [ABSTRACT FROM AUTHOR]

Snakebite envenomation is a serious health concern in tropical regions, resulting in high mortality. The World Health Organization (WHO) has declared it a neglected tropical disease and is working on strategies to reduce mortality. Russell's viper (Daboia russelii) is one of the most abundant venomous snakes found across Southeast Asia. Proteomic analysis of Russell's viper venom has demonstrated variation, with phospholipase A2 (PLA2) being the most abundant toxin across geographic boundaries. PLA2, a major constituent of the low-molecular-weight fraction of snake venom, hydrolyses phospholipids at the sn-2 position, releasing arachidonic acid and lysophospholipids. They are reported to cause various pharmacological effects, including hemolysis, anticoagulation, neurotoxicity, myotoxicity, and oedema. Though administration of antivenoms (ASV) is the primary treatment for envenomation, it has many drawbacks. Besides causing hypersensitivity reactions and life-threatening anaphylaxis, treatment with ASV is further complicated due to its inability to neutralize low-molecular-weight toxins. Thus, there is a greater need to produce next-generation antivenoms that can target specific toxins in the venom. In this review, we explored the classification of Russell's viper and the variation in its proteomic profile across Southeast Asia to date. In addition, we have also summarized the mechanism of action of PLA2 and discussed various isoforms of PLA2 found across different regions with their respective pharmacological effects. Finally, the drawbacks of commercially available antivenoms and the molecules investigated for inhibiting the low-molecular-weight toxin, PLA2 are discussed. [ABSTRACT FROM AUTHOR]

Snake venoms are complex mixtures of toxic proteins that hold significant medical, pharmacological and evolutionary interest. To better understand the genetic diversity underlying snake venoms, we developed VenomCap, a novel exon‐capture probe set targeting toxin‐coding genes from a wide range of elapid snakes, with a particular focus on the ecologically diverse and medically important subfamily Hydrophiinae. We tested the capture success of VenomCap across 24 species, representing all major elapid lineages. We included snake phylogenomic probes in the VenomCap capture set, allowing us to compare capture performance between venom and phylogenomic loci and to infer elapid phylogenetic relationships. We demonstrated VenomCap's ability to recover exons from ~1500 target markers, representing a total of 24 known venom gene families, which includes the dominant gene families found in elapid venoms. We find that VenomCap's capture results are robust across all elapids sampled, and especially among hydrophiines, with respect to measures of target capture success (target loci matched, sensitivity, specificity and missing data). As a cost‐effective and efficient alternative to full genome sequencing, VenomCap can dramatically accelerate the sequencing and analysis of venom gene families. Overall, our tool offers a model for genomic studies on snake venom gene diversity and evolution that can be expanded for comprehensive comparisons across the other families of venomous snakes. [ABSTRACT FROM AUTHOR]

Toxocariasis is a zoonotic parasitic infection with worldwide distribution and high impact on human health. It has a limited clinical resolution with the available drugs, making it challenging to treat. Quercetin, which possesses biological and pharmacological qualities including antiparasitic, antioxidant, and anticancer activities, is a possible substitute for the current medications. Marine invertebrates can produce a vast array of different molecules, many of which are biologically active substances with distinct characteristics. In this study, we assessed the in vitro nematocidal effect of both quercetin and venom of Cassiopea andromeda Research highlights: Biological activity of quercetin could be used as chemotherapy for larval stages of parasitic nematode.Bioactive products in jellyfish venom is positively affect the larval stage of Toxocara. [ABSTRACT FROM AUTHOR]

Prevalent worldwide, the Androctonus scorpion genus contributes a vital role in scorpion envenoming. While diverse scorpionisms are observed because of several different species, their secretions to protect themselves have been identified as a potent source of antimicrobial peptide (AMP)‐like compounds. Distinctly, the venom of these species contains around 24 different AMPs, with definite molecules studied for their therapeutic potential as antimicrobial, antifungal, antiproliferative and antiangiogenic agents. Our review focuses on the therapeutic potential of native and synthetic AMPs identified so far in the Androctonus scorpion genus, identifying research gaps in peptide therapeutics and guiding further investigations. Certain AMPs have demonstrated remarkable compatibility to be prescribed as anticancer drug to reduce cancer cell proliferation and serve as a potent antibiotic alternative. Besides, analyses were performed to explore the characteristics and affinities of peptides for membranes. Overall, the study of AMPs derived from the Androctonus scorpion genus provides valuable insights into their potential applications in medicine and drug development. [ABSTRACT FROM AUTHOR]

Background: The snake genera Atropoides, Cerrophidion, and Metlapilcoatlus form a clade of neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion, and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib. Results: All venoms showed myotoxic and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenom ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2 inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types. Conclusions: This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms. [ABSTRACT FROM AUTHOR]

Scorpion venom may include pharmacological substances that have the potential to provide benefits. Multiple scientific investigations have shown that particular scorpion venoms induce apoptosis and inhibit the development of cancerous cells. The present study investigated the potential anticancer properties of the crude venom derived from Hottentotta saulcyi (H. saulcyi) on both in vivo mice models and in vitro breast carcinoma cells. The venom of scorpions belonging to the species H. saulcyi was obtained with the application of electrical stimulation at voltages of 8 and 10 V. The determination of the Average Lethal Dose 50 (LD50) was conducted. The present work assessed the in vitro cytotoxicity and morphological characteristics of H. saulcyi venom using fluorescence microscopy, MTT assay, and flow cytometry assessment. Additionally, research was performed to assess the cytotoxic effects in vivo on a mouse model with breast cancer. The examination of MCF-7 cells treated with scorpion venom at a microscopic level revealed the existence of cells undergoing apoptosis. The venom of H. saulcyi has anticancer properties, as shown by the observation that MCF-7 cells had a 62.12% apoptotic rate when exposed to a dose of 1.47 mg/L. Based on the results obtained, it can be shown that the viability of MCF-7 cells has exhibited a substantial reduction (P < 0.01). Furthermore, the findings indicated that the venom of H. saulcyi resulted in a significant increase in the synthesis of TNF-α, IL-6, IL-10, TGF-β, and caspase (P < 0.05). The treatment groups administered with H. saulcyi venom exhibited a significant augmentation in the expression of proapoptotic genes compared to the control group of healthy individuals. The transcription of the BCL2 gene exhibited a statistically significant increase in the healthy control group compared to both the healthy venom-treated group (P < 0.05) and the malignant venom-treated group (P < 0.01). The crude venom of H. saulcyi has considerable promise in demonstrating anticancer properties. Further investigation may be warranted to explore the potential of using H. saulcyi crude venom as a medicinal platform for the prevention of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Variation in snake venoms is well documented, both between and within species, with intraspecific venom variation often correlated with geographically distinct populations. The puff adder, Bitis arietans, is widely distributed across sub-Saharan Africa and into the Arabian Peninsula where it is considered a leading cause of the ~310,000 annual snakebites across the region, with its venom capable of causing substantial morbidity and mortality. Despite its medical importance and wide geographic distribution, there is little known about venom variation between different B. arietans populations and the potential implications of this variation on antivenom efficacy. Methodology: We applied a range of analyses, including venom gland transcriptomics, in vitro enzymatic assays and reverse phase chromatography to comparatively analyse B. arietans venoms originating from Nigeria, Tanzania, and South Africa. Immunological assays and in vitro enzymatic neutralisation assays were then applied to investigate the impact of venom variation on the potential efficacy of three antivenom products; SAIMR Polyvalent, EchiTAb-Plus and Fav-Afrique. Findings: Through the first comparison of venom gland transcriptomes of B. arietans from three geographically distinct regions (Nigeria, Tanzania, and South Africa), we identified substantial variation in toxin expression. Findings of venom variation were further supported by chromatographic venom profiling, and the application of enzymatic assays to quantify the activity of three pathologically relevant toxin families. However, the use of western blotting, ELISA, and in vitro enzymatic inhibition assays revealed that variation within B. arietans venom does not appear to substantially impact upon the efficacy of three African polyvalent antivenoms. Conclusions: The large distribution and medical importance of B. arietans makes this species ideal for understanding venom variation and the impact this has on therapeutic efficacy. The findings in this study highlight the likelihood for considerable venom toxin variation across the range of B. arietans, but that this may not dramatically impact upon the utility of treatment available in the region. Author summary: The puff adder (Bitis arietans) is found across sub-Saharan Africa and the Arabian Peninsula and is capable of causing life threatening pathology due to its potent venom. The extensive range of B. arietans exposes populations to different ecological pressures which may impact upon the composition of venom toxins. In this study, we examined the venom composition of B. arietans from three countries separated by large geographic distance: Nigeria, Tanzania and South Africa. By integrating venom gland transcriptomes, venom chromatography, and in vitro functional assays to profile B. arietans venom composition, we uncovered extensive variation between the three locales. Given that venom variation can have a significant impact on the efficacy of antivenom treatment, we also investigated the ability of three African antivenoms to recognise and inhibit in vitro venom activity. Through these analyses, we were able to determine that venom variation did not have a substantial impact on the neutralising effect of selected antivenoms. This study has highlighted the potentially extensive venom variation found across the range of B. arietans and initiated valuable investigations into the efficacy of African antivenoms to protect human populations vulnerable to snakebite envenoming. [ABSTRACT FROM AUTHOR]

Venoms are complex mixtures produced by animals and consist of hundreds of components including small molecules, peptides, and enzymes selected for effectiveness and efficacy over millions of years of evolution. With the development of venomics, which combines genomics, transcriptomics, and proteomics to study animal venoms and their effects deeply, researchers have identified molecules that selectively and effectively act against membrane targets, such as ion channels and G protein-coupled receptors. Due to their remarkable physico-chemical properties, these molecules represent a credible source of new lead compounds. Today, not less than 11 approved venom-derived drugs are on the market. In this review, we aimed to highlight the advances in the use of venom peptides in the treatment of diseases such as neurological disorders, cardiovascular diseases, or cancer. We report on the origin and activity of the peptides already approved and provide a comprehensive overview of those still in development. [ABSTRACT FROM AUTHOR]

Background: Two strains of the endoparasitoid Cotesia typhae (Hymenoptera: Braconidae) present a differential parasitism success on the host, Sesamia nonagrioides (Lepidoptera: Noctuidae). One is virulent on both permissive and resistant host populations, and the other only on the permissive host. This interaction provides a very interesting frame for studying virulence factors. Here, we used a combination of comparative transcriptomic and proteomic analyses to unravel the molecular basis underlying virulence differences between the strains. Results: First, we report that virulence genes are mostly expressed during the pupal stage 24 h before adult emergence of the parasitoid. Especially, 55 proviral genes are up-regulated at this stage, while their expression is only expected in the host. Parasitoid gene expression in the host increases from 24 to 96 h post-parasitism, revealing the expression of 54 proviral genes at early parasitism stage and the active participation of teratocytes to the parasitism success at the late stage. Secondly, comparison between strains reveals differences in venom composition, with 12 proteins showing differential abundance. Proviral expression in the host displays a strong temporal variability, along with differential patterns between strains. Notably, a subset of proviral genes including protein-tyrosine phosphatases is specifically over-expressed in the resistant host parasitized by the less virulent strain, 24 h after parasitism. This result particularly hints at host modulation of proviral expression. Combining proteomic and transcriptomic data at various stages, we identified 8 candidate genes to support the difference in reproductive success of the two strains, one proviral and 7 venom genes, one of them being also produced within the host by the teratocytes. Conclusions: This study sheds light on the temporal expression of virulence factors of Cotesia typhae, both in the host and in the parasitoid. It also identifies potential molecular candidates driving differences in parasitism success between two strains. Together, those findings provide a path for further exploration of virulence mechanisms in parasitoid wasps, and offer insights into host-parasitoid coevolution. [ABSTRACT FROM AUTHOR]

Apitherapy has started to gain tremendous recognition because of extraordinary pharmacological importance of honeybee‐related ingredients and their derivatives. There has been a renewed interest in the bee venom–based therapies. Interdisciplinary researchers are studying the chemistry and translational value of venom for effective cancer treatment. Bee venom and its major component, melittin, are cytotoxic in cancer cells. In this study, MTT and scratch assays were performed for analysis of melittin‐mediated antimetastatic effects. QPCR was used for expression profiling of metastasis‐related genes. Three anti‐metastatic genes (BRMS1, DRG1, and KAI1/CD82) were studied for the first time after bee venom and melittin treatment in MDA‐MB‐231 breast cancer cells compared with normal breast cells, and two prometastatic genes (EGFR and WNT7B) were also examined. KAI1/CD82 and BRMS1 are the negative regulators of EGFR. WNT7B is a negative regulator of KAI1/CD82. Selective cytotoxicity of bee venom and melittin was found to be higher as compared to cisplatin. Melittin induced an increase in the expression of BRMS1 and DRG1, whereas bee venom upregulated DRG1 and KAI1/CD82 expression in breast cancer. WNT7B was downregulated in bee venom–treated breast cancer cells. Results suggested that bee venom/melittin exerted antimetastatic effects primarily through upregulation of BRMS1, DRG1, and KAI1/CD82, and downregulation of WNT7B. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated the nematocyst types found in the tentacles of box jellyfish Gershwinia thailandensis and Morbakka sp. in Thai waters, providing detailed taxonomic insights into these toxic stinging cells. Three nematocyst types were identified in both species: club-shaped microbasic p-mastigophores (Type 4), oval isorhizas, and oval microbasic p-rhopaloids. While the sizes of nematocyst capsules varied between species, the spination pattern of discharge tubules was consistent. These differences in nematocyst types, population densities, and morphologies may indicate evolutionary adaptations and functional specialization. Understanding these distinctions could aid in developing species-specific envenomation treatments and deepen our knowledge of the ecological and toxicological roles of these nematocysts. Further research on the molecular composition and venom release mechanisms will offer valuable biological insights. Nematocysts, specialized stinging cells in cnidarians, play a crucial role in both defense and prey capture, containing venomous, coiled tubes within a capsule. While box jellyfish are recognized as a medical threat, information on the nematocysts of species like Gershwinia thailandensis and Morbakka sp. from Thai waters remains sparse. This study explores the types and morphology of nematocysts found in the tentacles of these species using light and scanning electron microscopy. We identified three nematocyst types: club-shaped microbasic p-mastigophores, oval isorhizas, and oval microbasic p-rhopaloids. Notably, significant differences in capsule sizes were observed, especially in the microbasic p-mastigophores and isorhizas. The discharge tubules tapered from the proximal to the distal ends, featuring arrow-shaped spines in a helical pattern. A distinct lancet structure was present in both microbasic p-mastigophores and p-rhopaloids. These findings suggest that variations in nematocyst size and morphology may be linked to evolutionary adaptations, functional roles, and venom toxicity. Further research into venom discharge mechanisms could offer valuable insights into the ecological and medical importance of these cnidarians. [ABSTRACT FROM AUTHOR]

Within the phylum Cnidaria, sea anemones (class Anthozoa) express a rich diversity of ion-channel peptide modulators with biomedical applications, but corollary discoveries from jellyfish (subphylum Medusozoa) are lacking. To bridge this gap, bioactivities of previously unexplored proteinaceous and small molecular weight (~15 kDa to 5 kDa) venom components were assessed in a mouse dorsal root ganglia (DRG) high-content calcium-imaging assay, known as constellation pharmacology. While the addition of crude venom led to nonspecific cell death and Fura-2 signal leakage due to pore-forming activity, purified small molecular weight fractions of venom demonstrated three main, concentration-dependent and reversible effects on defined heterogeneous cell types found in the primary cultures of mouse DRG. These three phenotypic responses are herein referred to as phenotype A, B and C: excitatory amplification (A) or inhibition (B) of KCl-induced calcium signals, and test compound-induced disturbances to baseline calcium levels (C). Most notably, certain Alatina alata venom fractions showed phenotype A effects in all DRG neurons; Physalia physalis and Chironex fleckeri fractions predominantly showed phenotype B effects in small- and medium-diameter neurons. Finally, specific Physalia physalis and Alatina alata venom components induced direct excitatory responses (phenotype C) in glial cells. These findings demonstrate a diversity of neuroactive compounds in jellyfish venom potentially targeting a constellation of ion channels and ligand-gated receptors with broad physiological implications. [ABSTRACT FROM AUTHOR]

A comprehensive LC-MS study examined the venom components of the solitary scoliid wasp Scolia oculata. Online mass fingerprinting showed that crude venom contains 25 small molecules (amino acids, biogenic amines, and nucleosides/nucleotides) and 45 peptides with MW 400-2700. The small molecules were identified by elemental composition analysis, and peptide sequences were determined by ESI-MS/MS and MALDI-TOF/TOF MS analyses. As major peptide components, a known peptide, β-scoliidine (DYVTVKGFSPLRKA), and three new peptides, γ-scoliidine (YVTVKGFSPLR), δ-scoliidine (YVTVKGFSPLREP) and ε-scoliidine (DYVTVKGFSPLREP) were identified, all of which are closely homologous to each other. Once the neuroprotective effects of β-scoliidine have already been described, the other three new scoliidine peptides were analyzed against oxidative stress-induced toxicity in PC12 neuronal cells by mitochondrial metabolism assay, and the structure-activity relationship was evaluated. Interestingly, pre-treatment with ε-scoliidine increased the mitochondrial metabolism of PC12 cells (106 ± 3.6%; p = 0.007) exposed to H2O2-induced oxidative stress in contrast to γ- and δ-scoliidines (77.6 ± 4.8 and 68.5 ± 4.1%, respectively) in compared to cells treated only H2O2 (75.8 ± 2.4%). These new peptides were also analyzed for enzyme inhibitor/substrate assays with angiotensin-converting enzyme (ACE), neprilysin (NEP), and acetylcholinesterase (AChE). In these assays, only δ- and ε-scoliidines increased the AChE activity (128.7 ± 3.8%; p = 0.01; and 116.8 ± 3.8% p = 0.03; respectively) in relation to basal activity (100.1 ± 1.6%). In addition, the four peptides were analyzed through in silico analysis, and none of them demonstrated possible hemolytic and toxic activities. In our study, the comprehensive LC-MS and MS/MS analyses of Scolia oculate venom identified four major peptide components of the venom β-, γ-, δ- and ε-scoliidines, and small differences in their primary structures are important to their neuroprotective properties. [ABSTRACT FROM AUTHOR]

"True" cobras (genus Naja) are among the venomous snakes most frequently involved in snakebite accidents in Africa and Asia. The Cape cobra (Naja nivea) is one of the African cobras of highest medical importance, but much remains to be learned about its venom. Here, we used a shotgun proteomics approach to better understand the qualitative composition of N. nivea venom and tested its cytotoxicity and protease activity as well as its effect on intracellular Ca2+ release and NO synthesis. We identified 156 venom components representing 17 protein families, with the dominant ones being three-finger toxins, mostly of the short-chain type. Two-thirds of the three-finger toxin entries identified were assigned as cytotoxins, while the remainder were categorized as neurotoxins, including short-chain, long-chain, and ancestral three-finger toxins. We also identified snake venom metalloproteinases and members of CRISP, l-amino acid oxidase, and other families. Protease activity and its effect on intracellular Ca2+ release and NO synthesis were low. Phospholipase A2 activity was surprisingly high, despite this toxin family being marginally recovered in the analyzed venom. Cytotoxicity was relevant only at higher venom concentrations, with macrophage and neuroblastoma cell lines showing the lowest viability. These results are in line with the predominantly neurotoxic envenomation symptoms caused by Cape cobra bites. The present overview of the qualitatively complex and functionally intriguing venom of N. nivea may provide insights into the pathobiochemistry of this species' venom. [ABSTRACT FROM AUTHOR]

This study explores the potential of natural bioactive peptides from animal venoms as targeted anti-cancer agents with reduced toxicity. Initially, we screened a broad collection of animal venoms for their antiproliferative activity against cancer cell lines. From this collection, we selected venoms from Naja anchietae and Naja senegalensis due to their promising activity. Utilizing reverse- phase high-performance liquid chromatography (RP HPLC), mass spectrometry (MALDI-TOF MS and MALDI-TOF TOF MSMS), and Edman degradation sequencing, we isolated and characterized three peptides named CTNanc1, CTNanc2, and CTNanc3 from Naja anchietae, and three others named CTNsen1, CTNsen2, and CTNsen3 from Naja senegalensis, each with a molecular weight of around 7 kDa. These purified peptides demonstrated inhibition of U87 glioblastoma cell proliferation, but not of U251 and T98G cells, in cell viability assays. To assess the impact of these treatments on cell viability, apoptosis, and necrosis, flow cytometry assays were conducted on U87 cells at 72 h. The results showed a decrease in cell viability and an increase in dead cells, suggesting that the treatments not only promote apoptosis, but may also lead to increased necrosis or late-stage apoptosis as the exposure time increases. These findings suggest that these peptides could be developed as leads for cancer therapy. [ABSTRACT FROM AUTHOR]

Australian elapid snake venoms are uniquely procoagulant, utilizing blood clotting enzyme Factor Xa (FXa) as a toxin, which evolved as a basal trait in this clade. The subsequent recruitment of Factor Va (FVa) as a toxin occurred in the last common ancestor of taipans (Oxyuranus species) and brown snakes (Pseudonaja species). Factor II (prothrombin) activation has been stated as the primary mechanism for the lethal coagulopathy, but this hypothesis has never been tested. The additional activation of Factor VII (FVII) by Oxyuranus/Pseudonaja venoms has historically been considered as a minor, unimportant novelty. This study aimed to investigate the significance of toxic FVII activation relative to prothrombin activation by testing a wide taxonomical range of Australian elapid species with procoagulant venoms. The activation of FVII or prothrombin, with and without the Factor Va as a cofactor, was assessed, along with the structural changes involved in these processes. All procoagulant species could activate FVII, establishing this as a basal trait. In contrast, only some lineages could activate prothrombin, indicating that this is a derived trait. For species able to activate both zymogens, Factor VII was consistently more strongly activated than prothrombin. FVa was revealed as an essential cofactor for FVII activation, a mechanism previously undocumented. Species lacking FVa in their venom utilized endogenous plasma FVa to exert this activity. The ability of the human FXa:FVa complex to activate FVII was also revealed as a new feedback loop in the endogenous clotting cascade. Toxin sequence analyses identified structural changes essential for the derived trait of prothrombin activation. This study presents a paradigm shift in understanding how elapid venoms activate coagulation factors, highlighting the critical role of FVII activation in the pathophysiological effects upon the coagulation cascade produced by Australian elapid snake venoms. It also documented the novel use of Factor Va as a cofactor for FVII activation for both venom and endogenous forms of FXa. These findings are crucial for developing better antivenoms and treatments for snakebite victims and have broader implications for drug design and the treatment of coagulation disorders. The research also advances the evolutionary biology knowledge of snake venoms. [ABSTRACT FROM AUTHOR]

Honeybee venom (apitoxin), composed of bioactive components such as melittin, apamin, and phospholipase A2, has been used in traditional medicine for centuries. Modern research explores its potential therapeutic applications for various diseases. Clinical studies and preclinical research have demonstrated its efficacy in treating conditions like rheumatoid arthritis, osteoarthritis, neurological disorders, and cancer. Despite its therapeutic potential, bee venom carries risks, including allergic reactions. Advances in synthetic venom production offer promising alternatives for broader and safer clinical applications. While more large-scale clinical trials are needed to confirm its efficacy and safety, honeybee venom remains a compelling candidate for novel treatments across a wide range of diseases. [ABSTRACT FROM AUTHOR]

Maurotoxin (MTX) is a 34-residue peptide from Scorpio maurus venom. It is reticulated by four disulfide bridges with a unique arrangement compared to other scorpion toxins that target potassium (K+) channels. Structure–activity relationship studies have not been well performed for this toxin family. The screening of Scorpio maurus venom was performed by different steps of fractionation, followed by the ELISA test, using MTX antibodies, to isolate an MTX-like peptide. In vitro, in vivo and computational studies were performed to study the structure–activity relationship of the new isolated peptide. We isolated a new peptide designated MTX1, structurally related to MTX. It demonstrated toxicity on mice eight times more effectively than MTX. MTX1 blocks the Kv1.2 and Kv1.3 channels, expressed in Xenopus oocytes, with IC50 values of 0.26 and 180 nM, respectively. Moreover, MTX1 competitively interacts with both 125I-apamin (IC50 = 1.7 nM) and 125I-charybdotoxin (IC50 = 5 nM) for binding to rat brain synaptosomes. Despite its high sequence similarity (85%) to MTX, MTX1 exhibits a higher binding affinity towards the Kv1.2 and SKCa channels. Computational analysis highlights the significance of specific residues in the β-sheet region, particularly the R27, in enhancing the binding affinity of MTX1 towards the Kv1.2 and SKCa channels. [ABSTRACT FROM AUTHOR]

ω-Grammotoxin-SIA (GrTX-SIA) was originally isolated from the venom of the Chilean rose tarantula and demonstrated to function as a gating modifier of voltage-gated Ca2+ (CaV) channels. Later experiments revealed that GrTX-SIA could also inhibit voltage-gated K+ (KV) channel currents via a similar mechanism of action that involved binding to a conserved S3-S4 region in the voltage-sensing domains (VSDs). Since voltage-gated Na+ (NaV) channels contain homologous structural motifs, we hypothesized that GrTX-SIA could inhibit members of this ion channel family as well. Here, we show that GrTX-SIA can indeed impede the gating process of multiple NaV channel subtypes with NaV1.6 being the most susceptible target. Moreover, molecular docking of GrTX-SIA onto NaV1.6, supported by a p.E1607K mutation, revealed the voltage sensor in domain IV (VSDIV) as being a primary site of action. The biphasic manner in which current inhibition appeared to occur suggested a second, possibly lower-sensitivity binding locus, which was identified as VSDII by using KV2.1/NaV1.6 chimeric voltage-sensor constructs. Subsequently, the NaV1.6p.E782K/p.E838K (VSDII), NaV1.6p.E1607K (VSDIV), and particularly the combined VSDII/VSDIV mutant lost virtually all susceptibility to GrTX-SIA. Together with existing literature, our data suggest that GrTX-SIA recognizes modules in NaV channel VSDs that are conserved among ion channel families, thereby allowing it to act as a comprehensive ion channel gating modifier peptide. [ABSTRACT FROM AUTHOR]

Background: The venom of Bothrops lanceolatus, a viperid species endemic to the Lesser Antillean Island of Martinique, induces thrombosis in a number of patients. Previous clinical observations indicate that thrombotic events are more common in patients bitten by juvenile specimens. There is a need to develop an experimental model of this effect in order to study the mechanisms involved. Methodology/Principal findings: The venoms of juvenile and adult specimens of B. lanceolatus were compared by (a) describing their proteome, (b) assessing their ability to induce thrombosis in a mouse model, and (c) evaluating their in vitro procoagulant activity and in vivo hemostasis alterations. Venom proteomes of juvenile and adult specimens were highly similar, albeit showing some differences. When injected by the intraperitoneal (i.p.) route, the venom of juvenile specimens induced the formation of abundant thrombi in the pulmonary vasculature, whereas this effect was less frequent in the case of adult venom. Thrombosis was not abrogated by the metalloproteinase inhibitor Batimastat. Both venoms showed a weak in vitro procoagulant effect on citrated mouse plasma and bovine fibrinogen. When administered intravenously (i.v.) venoms did not affect classical clotting tests (prothrombin time and activated partial thromboplastin time) but caused a partial drop in fibrinogen concentration. The venom of juvenile specimens induced partial alterations in some rotational thromboelastometry parameters after i.v. injection. When venoms were administered i.p., only minor alterations in classical clotting tests were observed with juvenile venom, and no changes occurred for either venom in rotational thromboelastometry parameters. Both juvenile and adult venoms induced a marked thrombocytopenia after i.p. injection. Conclusions/Significance: An experimental model of the thrombotic effect induced by B. lanceolatus venom was developed. This effect is more pronounced in the case of venom of juvenile specimens, despite the observation that juvenile and adult venom proteomes are similar. Adult and juvenile venoms do not induce a consumption coagulopathy characteristic of other Bothrops sp venoms. Both venoms induce a conspicuous thrombocytopenia. This experimental model reproduces the main clinical findings described in these envenomings and should be useful to understand the mechanisms of the thrombotic effect. Author summary: Envenomings by the viperid species Bothrops lanceolatus, endemic of the Caribbean Island of Martinique, are characterized by a thrombotic effect responsible for infarcts in various organs. Until now, no experimental in vivo models of this effect have been described. In this study, we developed a mouse model of thrombosis by using the intraperitoneal route of venom injection. The venom of juvenile specimens of B. lanceolatus induced the formation of abundant thrombi in the lungs, whereas the effect was much less pronounced with the venom of adult specimens. This difference in the ability of juvenile and adult venoms occurs despite both venoms having highly similar proteomic profiles. Both adult and juvenile venoms showed a weak in vitro procoagulant effect on plasma and fibrinogen, underscoring a thrombin-like (pseudo-procoagulant) activity. In vivo, the venoms did not affect the classical clotting tests (prothrombin time and activated partial thromboplastin time) but induced a partial drop in fibrinogen concentration and limited alterations in rotational thromboelastometry parameters when injected by the i.v. route. In contrast, few alterations of these parameters were observed after i.p. injection of venoms, in conditions in which thrombosis occurred, hence evidencing the lack of a consumption coagulopathy. After i.p. injection both venoms induced a pronounced thrombocytopenia. This experimental model reproduces some of the main clinical manifestations of envenoming by this species. This model can be used to identify the toxins responsible for the thrombotic effect, to study the mechanism(s) of thrombosis and to assess the preclinical efficacy of antivenoms and novel therapies. [ABSTRACT FROM AUTHOR]

The genus Mixcoatlus is composed of three species: Mixcoatlus barbouri , M. browni , and M. melanurus , of which the venom composition of M. melanurus , the most common species of the three, has only recently been described. However, very little is known about the natural history of M. barbouri and M. browni , and the venom composition of these two species has remained thus far unexplored. In this study we characterize the proteomic profiles and the main biochemical and toxic activities of these two venoms. Proteomic data obtained by shotgun analysis of whole venom identified 12 protein families for M. barbouri , and 13 for M. browni. The latter venom was further characterized by using a quantitative 'venomics' protocol, which revealed that it is mainly composed of 51.1 % phospholipases A 2 (PLA 2), 25.5 % snake venom serine proteases (SVSP), 4.6 % l -amino oxidases (LAO), and 3.6 % snake venom metalloproteases (SVMP), with lower percentages other six protein families. Both venoms contained homologs of the basic and acidic subunits of crotoxin. However, due to limitations in M. barbouri venom availability, we could only characterize the crotoxin-like protein of M. browni venom, which we have named Mixcoatlutoxin. It exhibited a lethal potency in mice like that described for classical rattlesnake crotoxins. These findings expand knowledge on the distribution of crotoxin-like heterodimeric proteins in viper snake species. Further investigation of the bioactivities of the venom of M. barbouri , on the other hand, remains necessary. [Display omitted] • The first proteomic characterization of Mixcoatlus browni and M. barbouri venoms is reported. • A new Crotoxin-like protein in the venom of Mixcoatlus browni is characterized. • Mixcoatlus barbouri venom contains homologs of acidic and basic subunits of Crotoxin. • The Antivipmyn antivenom can neutralize the lethality of M. browni. [ABSTRACT FROM AUTHOR]

In Brazil, around 80% of snakebites are caused by snakes of the genus Bothrops. A three-dimensional culture model was standardized and used to perform treatments with Bothrops erythromelas venom (BeV) and its antivenom (AV). The MRC-5 and L929 cell lines were cultured at increasing cell densities. Morphometric parameters were evaluated through images obtained from an inverted microscope: solidity, circularity, and Feret diameter. L929 microtissues (MT) showed better morphometric data, and thus they were used for further analysis. MT viability was assessed using the acridine orange and ethidium bromide staining method, which showed viable cells in the MT on days 5, 7, and 10 of cultivation. Histochemical and histological analyses were performed, including hematoxylin/eosin staining, which showed a good structure of the spheroids. Alcian blue staining revealed the presence of acid proteoglycans. Immunohistochemical analysis with ki-67 showed different patterns of cell proliferation. The MT were also subjected to pharmacological tests using the BeV, in the presence or absence of its AV. The results showed that the venom was not cytotoxic, but it caused morphological changes. The MT showed cell detachment, losing their structure. The antivenom was able to partially prevent the venom activities. [ABSTRACT FROM AUTHOR]

Snake venoms are complex mixtures majorly composed of proteins with well-studied biological effects. However, the exploration of non-protein components, especially lipids, remains limited despite their potential for discovering bioactive molecules. This study compares three liquid–liquid lipid extraction methods for both chemical and biological analyses of Bothrops moojeni snake venom. The methods evaluated include the Bligh and Dyer method (methanol, chloroform, water), considered standard; the Acunha method, a modification of the Bligh and Dyer protocol; and the Matyash method (MTBE/methanol/water), featuring an organic phase less dense than the aqueous phase. Lipidomic analysis using liquid chromatography with high-resolution mass spectrometry (LC-HRMS) system revealed comparable values of lipid constituents' peak intensity across different extraction methods. Our results show that all methods effectively extracted a similar quantity of lipid species, yielding approximately 17–18 subclasses per method. However, the Matyash and Acunha methods exhibited notably higher proportions of biologically active lipids compared to the Bligh and Dyer method, particularly in extracting lipid species crucial for cellular structure and function, such as sphingomyelins and phosphatidylinositol-phosphate. In conclusion, when selecting a lipid extraction method, it is essential to consider the study's objectives. For a biological approach, it is crucial to evaluate not only the total quantity of extracted lipids but also their quality and biological activity. The Matyash and Acunha methods show promise in this regard, potentially offering a superior option for extracting biologically active lipids compared to the Bligh and Dyer method. [ABSTRACT FROM AUTHOR]

Aim: To study the safety profile and effectiveness of Anti Snake venom (ASV) in western India Methods: This retrospective study gathered safety, and clinicoepidemiologicaldata on 157 patients admitted at Shri Sainath Hospital, Dharampur, Gujarat, from July 2022 to February 2023. Results: Majority were bitten between August and November. There were 88 males, 5 to70 yrs. (mean 39.14), 69 females, 2 to 70 years (mean 40.32). 6 of these were children ranging from 2 to 12 years.134 were agricultural labourers. 120 cases were analysable. 17 had neurotoxicity and 103 had haemotoxicity. Mean (SD) number of vials used was 10.1(6.2), time to discontinue ASV was 3.0(5.2) hours, and duration of hospital stay was 4.5(2.6) days. Patients bitten by saw scaled vipers were discharged early. In Russel’s Viper bites, number of vials used, was higher if the bite to needle time was less than 6 hours 9 patients suffered 24 adverse events, with two possible cases of anaphylaxis. One case had urticaria, itching and tachycardia as a triad. The remaining were isolated events of mild urticaria, itching, tachycardia, hypotension, cough, rigor. Conclusion: 10.1 vials were needed on average for control of envenomation with no fatalities or severe comorbidities. Adverse events were reported in 5.7% cases. The ASV brand used was well tolerated. Patients who were brought late suffered more renal complications [ABSTRACT FROM AUTHOR]

The venom contained within cnidarian nematocysts has a complex composition and holds significant potential for biotechnological applications. In this context, one of the most effective methods for studying nematocyst contents is the proteomic approach, which can detect even trace amounts of compounds while minimizing the need for large-scale animal collection, thus helping to preserve ecosystem integrity. This study aimed to provide a comprehensive proteomic and biochemical characterization of the crude nematocyst extract from the common hydrozoan Velella velella. Despite not being harmful to humans, the analysis of the crude venom extract from V. velella brought to the identification of 783 different proteins, categorized into structural components, enzymes, and potential toxins, revealing a qualitative composition of the venom similar to that of other more toxic cnidarians. Biochemical assays confirmed the presence of various active hydrolytic enzymes within the extract, including proteases, phospholipases, hyaluronidases, DNases, and chitinases. These findings pave the road for future studies involving the pharmacological applications of Velella velella venom components through recombinant production and functional testing. [ABSTRACT FROM AUTHOR]

Snake bites are a global health hazard and are a noteworthy cause of mortality and morbidity especially in Southeast Asia. Cerebral complications after snake bite are rare. It can be attributed to various factors such as vasculitis, vasospasm, endothelial damage; toxin-induced procoagulant effect, and disseminated intravascular coagulation. We present a case of a previously healthy 22-year-old woman who suffered acute multiple cerebral infarctions following Russell's viper bite. Imaging revealed significant non-hemorrhagic infarctions in the left middle cerebral artery territory and right pons, indicating rare yet severe neurological complications of viper envenomation. The patient experienced serious complications including rhabdomyolysis and acute kidney injury, ultimately leading to her demise due to aspiration pneumonia and septic shock. This case underscores the potential neurological impact of viper envenomation and underscores the challenges in managing delayed procoagulant effects of snake venom, despite the administration of anti-snake venom. Early detection and intervention remain vital in addressing such devastating outcomes. [ABSTRACT FROM AUTHOR]

Featured Application: The application of this study is all computational studies considering venom peptides as potential sources of therapeutics. Animal venom has been gaining traction as a potential source of therapeutics for various diseases. Spiders encompass a wide variety of venom-producing species, of which tarantulas of the family Theraphosidae are widely known across the globe. Research towards tarantula venom therapeutics has led to its potential application as antinociceptives. Death receptors are cellular receptors that induce apoptosis—the body's natural suicide mechanism—to destroy malfunctioning cells. These are particularly of interest in cancer research, as this mechanism is tampered with, resulting in cancer cell proliferation. In this study, the viability of venom toxins from the Theraphosidae family of spiders to induce apoptosis by binding to human death receptors is investigated by carrying out anti-cancer screening, molecular docking, ADMET evaluation, then molecular dynamics and thermodynamic analysis twice, first to ascertain the best receptor–peptide systems per receptor, and secondly to more comprehensively describe binding stability and thermodynamics. Results point to favorable receptor–peptide interactions due to similarities in equilibrium behavior with the death ligand–death receptor systems, along with favorable end-state binding energies and ADMET analysis results. Further inquiry is recommended to assess the real-life efficacy and viability of theraphotoxins as apoptosis therapeutics and further improve on their ability to induce apoptosis. [ABSTRACT FROM AUTHOR]

Background Snake venom is a complex mixture of organic and inorganic constituents, including proteins and peptides. Several studies showed that antivenom efficacy differs due to intra- and inter-species venom variation. Methods In the current study, comparative functional characterization of major enzymatic proteins present in Craspedocephalus malabaricus and Daboia russelii venom was investigated through various in vitro and immunological cross-reactivity assays. Results The enzymatic assays revealed that hyaluronidase and phospholipase A2 activities were markedly higher in D. russelii. By contrast, fibrinogenolytic, fibrin clotting and L-amino acid oxidase activities were higher in C. malabaricus venom. ELISA results suggested that all the antivenoms had lower binding potential towards C. malabaricus venom. For D. russelii venom, the endpoint titration value was observed at 1:72 900 for all the antivenoms. In the case of C. malabaricus venom, the endpoint titration value was 1:2700, except for Biological E (1:8100). All these results, along with the avidity assays, indicate the strength of venom–antivenom interactions. Similarly, the western blot results suggest that all the antivenoms showed varied efficacies in binding and detecting the venom antigenic epitopes in both species. Conclusions The results highlight the need for species-specific antivenom to better manage snakebite victims. [ABSTRACT FROM AUTHOR]

The rise of biological invasions threatens biodiversity and food security, with the vespid family, including Vespa soror, being of particular concern. Our study focused on the alarm pheromone components of V. soror. By using gas chromatography‐mass spectrometry (GC‐MS) chemical analyses, electroantennograms, and field bioassays, we identified 5 compounds—2‐pentanol, 3‐methyl‐1‐butanol, 2‐heptanol, 2‐nonanol (2‐N), and isopentyl acetate (IPA)—in hornet sting venom that elicited defensive behavior from hornets. IPA and 2‐N also serve as alarm pheromone components in multiple honey bee species that are important prey for V. soror. This shared chemical signaling may allow cross‐detection by each species on the other's alarm cues. While it should be advantageous for bees to detect V. soror alarm pheromone, the benefits to V. soror of using IPA and 2‐N are unclear. V. soror may manipulate bee behavior, potentially distracting defenders, because they mark victim bee colonies by rubbing their abdomens, which contain their sting glands, at bee hive entrances. Our findings pose new evolutionary questions about the role of manipulation in the arms races. [ABSTRACT FROM AUTHOR]

Background: Herbal medicine has been used for the treatment of human and livestock ailments since ancient times. Numerous rural and urban communities in Ethiopia practice traditional medicine and transfer the knowledge verbally from generation to generation. Thus, this study was conducted to document the traditional medicinal plants and associated indigenous knowledge in Dibatie district, Metekel zone, Benishangul Gumuz Regional State, western Ethiopia. Methods: Three hundred seventy-four (374) informants from 11 kebeles (the smallest administrative units) were selected and participated in the data delivery. The ethnobotanical data collection was carried out using semi-structured interviews, preference ranking, direct matrix ranking, field observation, market surveys, and focus group discussions, including voucher specimen collections. The ethnobotanical data were analyzed using descriptive statistics (frequency and percentage), ranking, comparison, and quantitative ethnobotanical techniques such as informant consensus factor, fidelity level index, Jaccard's coefficient of similarity, and use value index. Results: A total of 170 plant species were recorded to treat 79 human and 29 livestock ailments. Fabaceae (with 20 species) and Asteraceae (with 18 species) were the most dominant medicinal plant families in the area. Most remedial plants were herbs (61 species, 35.88%), followed by shrubs (39 species, 22.94%). The majority (135 species, 79.41%) of medicinal plants were harvested from wild sources and mainly possessed multiple remedy parts (41.17%) that are usually prescribed in fresh form (60.13%). The most commonly reported human ailment was snake venom, while blackleg was mostly reported among livestock diseases. The herbal medicines were mostly administered orally (52.20%), followed by dermal (17.62%) application. Embelia schimperi Vatke, Glinus lotoides L., Haplosciadium abyssinicum Hochst., Mucuna melanocarpa Hochst. ex A. Rich., and Phragmanthera macrosolen (Steud. ex A. Rich.) M.G.Gilbert had the highest fidelity level values (100%) against the corresponding ailments. Conclusion: The study area is rich in a diversity of potential medicinal plants and associated indigenous knowledge. Thus, appropriate conservation actions and careful utilization are essential to counteract the rise of anthropogenic threats and to ensure the continuity of plants with the related indigenous knowledge. Additionally, the medicinal plants should be validated through experimentation to integrate local knowledge with modern medications. [ABSTRACT FROM AUTHOR]

Understanding the proximate and ultimate causes of phenotypic variation is fundamental in evolutionary research, as such variation provides the substrate for selection to act upon. Although trait variation can arise due to selection, the importance of neutral processes is sometimes understudied. We presented the first reference-quality genome of the Red Diamond Rattlesnake (Crotalus ruber) and used range-wide 'omic data to estimate the degree to which neutral and adaptive evolutionary processes shaped venom evolution. We characterized population structure and found substantial genetic differentiation across two populations, each with distinct demographic histories. We identified significant differentiation in venom expression across age classes with substantially reduced but discernible differentiation across populations. We then used conditional redundancy analysis to test whether venom expression variation was best predicted by neutral divergence patterns or geographically variable (a)biotic factors. Snake size was the most significant predictor of venom variation, with environment, prey availability, and neutral sequence variation also identified as significant factors, though to a lesser degree. By directly including neutrality in the model, our results confidently highlight the predominant, yet not singular, role of life history in shaping venom evolution. [ABSTRACT FROM AUTHOR]

The widespread geographical distribution of Russell's vipers (Daboia spp.) is associated with marked variations in the clinical outcomes of envenoming by species from different countries. This is likely to be due to differences in the quantity and potency of key toxins and, potentially, the presence or absence of some toxins in venoms across the geographical spectrum. In this study, we aimed to isolate and pharmacologically characterise the major neurotoxic components of D. siamensis venoms from Thailand and Java (Indonesia) and explore the efficacy of antivenom and a PLA2 inhibitor, Varespladib, against the neuromuscular activity. These data will provide insights into the link between venom components and likely clinical outcomes, as well as potential treatment strategies. Venoms were fractionated using RP-HPLC and the in vitro activity of isolated toxins assessed using the chick biventer cervicis nerve-muscle preparation. Two major PLA2 fractions (i.e., fractions 8 and 10) were isolated from each venom. Fraction 8 from both venoms produced pre-synaptic neurotoxicity and myotoxicity, whereas fraction 10 from both venoms was weakly neurotoxic. The removal of the two fractions from each venom abolished the in vitro neurotoxicity, and partially abolished myotoxicity, of the whole venom. A combination of the two fractions from each venom produced neurotoxic activity that was equivalent to the respective whole venom (10 µg/mL), but the myotoxic effects were not additive. The in vitro neurotoxicity of fraction 8 (100 nM) from each venom was prevented by the pre-administration of Thai Russell's viper monovalent antivenom (2× recommended concentration) or preincubation with Varespladib (100 nM). Additionally, the neurotoxicity produced by a combination of the two fractions was partially reversed by the addition of Varespladib (100–300 nM) 60 min after the fractions. The present study demonstrates that the in vitro skeletal muscle effects of Thai and Javanese D. siamensis venoms are primarily due to key PLA2 toxins in each venom. [ABSTRACT FROM AUTHOR]

Body temperature is primarily regulated by the hypothalamus, ensuring proper metabolic function. Envenomation by Phoneutria nigriventer can cause symptoms such as hypothermia, hyperthermia, sweating, and shivering, all related to thermoregulation. This study aims to analyze and identify components of the venom that affect thermoregulation and to evaluate possible mechanisms. Rats were used for thermoregulation analysis, venom fractionation by gel filtration and reverse-phase chromatography (C18), and sequencing by Edman degradation. The venom exhibited hypothermic effects in rats, while its fractions demonstrated both hypothermic (pool II) and hyperthermic (pool III) effects. Further separations of the pools with C18 identified specific peaks responsible for these effects. However, as the peaks were further purified, their effects became less significant. Tests on U87 human glioblastoma cells showed no toxicity. Sequencing of the most active peaks revealed masses similar to those of the Tachykinin and Ctenotoxin families, both known to act on the nervous system. The study concludes that molecules derived from venom can act synergistically or antagonistically. Additionally, toxins that affect thermoregulation are poorly studied and require further characterization. These toxins could potentially serve as sources for the development of new thermoregulatory drugs. [ABSTRACT FROM AUTHOR]

The Eastern Long-Nosed Viper (Vipera ammodytes meridionalis) is considered one of the most venomous snakes in Europe. However, it is unknown whether ontogenetic variation in venom effects occurs in this subspecies and how this may impact antivenom efficacy. In this study, we compared the procoagulant activities of V. a. meridionalis venom on human plasma between neonate and adult venom phenotypes. We also examined the efficacy of three antivenoms—Viperfav, ViperaTAb, and Inoserp Europe—across our neonate and adult venom samples. While both neonate and adult V. a. meridionalis venoms produced procoagulant effects, the effects produced by neonate venom were more potent. Consistent with this, neonate venom was a stronger activator of blood-clotting zymogens, converting them into their active forms, with a rank order of Factor X >> Factor VII > Factor XII. Conversely, the less potent adult venom had a rank order of FXII marginally more activated than Factor VII, and both much more so than Factor X. This adds to the growing body of evidence that activation of factors besides FII (prothrombin) and FX are significant variables in reptile venom-induced coagulopathy. Although all three examined antivenoms displayed effective neutralization of both neonate and adult V. a. meridionalis venoms, they generally showed higher efficacy on adult venom than on neonate venom. The ranking of antivenom efficacy against neonate venom, from the most effective to the least effective, were Viperfav, Inoserp Europe, ViperaTAb; for adult venom, the ranking was Inoserp Europe, Viperfav, ViperaTAb. Our data reveal ontogenetic variation in V. a meridionalis, but this difference may not be of clinical concern as antivenom was effective at neutralizing both adult and neonate venom phenotypes. Regardless, our results highlight a previously undocumented ontogenetic shift, likely driven by the documented difference in prey preference observed for this species across age classes [ABSTRACT FROM AUTHOR]

Snakebite envenoming (SBE) remains a severely neglected public health issue, particularly affecting tropical and subtropical regions, with Africa experiencing an estimated 435,000 to 580,000 snakebites annually, leading to high morbidity and mortality rates, especially across Africa and Asia. Recognized as a Neglected Tropical Disease, SBE management is further complicated by the inadequate efficacy of current antivenom treatments. Of particular concern are cobras (Naja sp.), whose neurotoxins can induce rapid fatal respiratory paralysis. In this study, we investigate the potential of nanobodies as a promising next-generation of immunotherapeutics against cobra venoms. Through a dual strategy of the characterization of venom toxic fractions from cobras captured for the first time in Algeria and Tunisia biotopes, coupled with in vitro assays to evaluate their interactions with acetylcholine receptors, and subsequent immunization of dromedaries to produce specific nanobodies, we identified two lethal fractions, F5 and F6, from each venom, and selected five nanobodies with significant binding and neutralizing of 3DL50 (0.74 mg/kg). The combination of these nanobodies demonstrated a synergistic effect, reaching 100% neutralizing efficacy of 2DL50 lethal venom fraction (0.88 mg/kg) doses in mice. Additionally, our findings highlighted the complex mechanism of cobra venom action through the lethal synergism among its major toxins. [ABSTRACT FROM AUTHOR]

Snakebite is a serious health issue in tropical and subtropical areas of the world and results in various pathologies, such as hemotoxicity, neurotoxicity, and local swelling, blistering, and tissue necrosis around the bite site. These pathologies may ultimately lead to permanent morbidity and may even be fatal. Understanding the chemical and biological properties of individual snake venom toxins is of great importance when developing a newer generation of safer and more effective snakebite treatments. Two main approaches to ionizing toxins prior to mass spectrometry (MS) analysis are electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI). In the present study, we investigated the use of both ESI-MS and MALDI-MS as complementary techniques for toxin characterization in venom research. We applied nanofractionation analytics to separate crude elapid venoms using reversed-phase liquid chromatography (RPLC) and high-resolution fractionation of the eluting toxins into 384-well plates, followed by online LC-ESI-MS measurements. To acquire clear comparisons between the two ionization approaches, offline MALDI-MS measurements were performed on the nanofractionated toxins. For comparison to the LC-ESI-MS data, we created so-called MALDI-MS chromatograms of each toxin. We also applied plasma coagulation assaying on 384-well plates with nanofractionated toxins to demonstrate parallel biochemical profiling within the workflow. The plotting of post-column acquired MALDI-MS data as so-called plotted MALDI-MS chromatograms to directly align the MALDI-MS data with ESI-MS extracted ion chromatograms allows the efficient correlation of intact mass toxin results from the two MS-based soft ionization approaches with coagulation bioassay chromatograms. This facilitates the efficient correlation of chromatographic bioassay peaks with the MS data. The correlated toxin masses from ESI-MS and/or MALDI-MS were all around 6–8 or 13–14 kDa, with one mass around 20 kDa. Between 24 and 67% of the toxins were observed with good intensity from both ionization methods, depending on the venom analyzed. All Naja venoms analyzed presented anticoagulation activity, whereas pro-coagulation was only observed for the Pseudonaja textillis venom. The data of MALDI-MS can provide complementary identification and characterization power for toxin research on elapid venoms next to ESI-MS. [ABSTRACT FROM AUTHOR]

Ophidism is a public health problem in tropical countries, occurring predominantly in rural areas. In Colombia, among the species responsible for snakebite envenomation, inflicting high mortality, is the Chocoan bushmaster, Lachesis acrochorda, better known locally by the names "verrugosa (warty)" and "pudridora (rot-causing)". In this research, the cardiotoxic effect of the venom of L. acrochorda in male Wistar rats weighing 230 ± 20 g was evaluated. A statistical design of randomized blocks was implemented with three treated groups, injected with lyophilized venom (doses of 3.22 μg/g, 6.43 μg/g, 12.86 μg/g), and a control group injected with 0.9% saline solution. Electrocardiographic (ECG) recordings were taken from the anesthetized animals, revealing an increase in the amplitude of the P and T waves and an increase in the duration of the QT intervals in the electrocardiographic recordings. These increases were not observed in the control biomodels. In the analysis of the CK and CK-MB enzyme levels, increases were also observed in the levels of cardiac isoenzymes in the injected animals, but none in the control animals. The histopathological analyses carried out reveal that the injected animals showed effects such as interfibrillar and perivascular edema, cellular shortening of the cardiomyocytes, foci with tissue destructuring, and necrosis with contraction bands. In conclusion, the venom of the Lachesis acrochorda snake increases the P and T waves and the QT interval and increases the CK and CK-MB enzymes in the blood. Additionally, it causes interfibrillar and perivascular edema in the cardiac tissue, cardiocytolysis, and contraction bands. [ABSTRACT FROM AUTHOR]

Apitoxin therapy (BVT—bee venom therapy) is an emerging complementary treatment utilizing bee venom for various medical conditions. This review explores the potential and therapeutic mechanisms of bee venom, focusing on its chemical composition and the methods for its extraction and purification to enhance safety while maintaining bioactivity. Bee venom contains amphipathic peptides such as melittin and apamin, enzymes like phospholipase A2, and bioamines including histamine and catecholamines, contributing to its pleiotropic effects. The therapeutic applications of bee venom span anti-inflammatory, analgesic, antimicrobial, antiviral, neuroprotective, anti-arthritic, and anti-cancer activities. Clinical and laboratory studies have demonstrated its efficacy in treating chronic and autoimmune diseases, pain management, and improving quality of life. The immunogenic properties of bee venom necessitate ongoing research to mitigate allergic reactions, ensuring its safe and effective use in medical practice. This review summarizes the current state of research on bee venom therapy, highlighting its potential benefits and future research directions. [ABSTRACT FROM AUTHOR]

Background: In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long‐term effectiveness of VIT. Methods: 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. Results: 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring‐Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p <.0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p <.0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V‐positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p <.01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p <.01). Conclusions: By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT. [ABSTRACT FROM AUTHOR]

The eastern small eyed snake (Cryptophis nigrescens; CN) is an uncommon cause of snakebite in Australia despite the widespread distribution of the snake along the east coast of Australia. Diagnosis of envenomation relies on identification of the snake which is often not possible with animal snakebite cases. This study examined the immunoreactivity profile of CN venom towards specific rabbit IgG made against the medically relevant snake venom immunotypes found in Australia (tiger, brown, black, death adder and taipan). A simultaneous sandwich ELISA format was used to quantify CN venom binding to venom specific Protein A purified rabbit IgG. The binding profiles demonstrated weak binding of CN venom to rabbit IgG made against both tiger (N. scutatus) and black snake (P. australis) venoms with approximately 0.19% and 0.069% cross reactivity, respectively. However, the concentration of venom likely to be present in the urine of CN envenomed patients and the low cross reactivity suggest that envenomed veterinary patients are unlikely to be detected in the commercial snake venom detection kit. It is possible that CN envenomation is more common but may be underdiagnosed where snake venom antigen detection is relied upon solely. Serum biochemical abnormalities also overlap with other snake species found in the same geographical area. In respect of antivenom therapy, administration of tiger snake antivenom is supported by the binding data, but due to the low cross reactivity multiple vials may be required. Limited clinical evidence also supports the efficacy of tiger snake antivenom for envenomation by CN. [ABSTRACT FROM AUTHOR]

We present genome assemblies for 18 snake species representing 18 families (Serpentes: Caenophidia): Acrochordus granulatus , Aparallactus werneri , Boaedon fuliginosus , Calamaria suluensis , Cerberus rynchops , Grayia smithii , Imantodes cenchoa , Mimophis mahfalensis , Oxyrhabdium leporinum , Pareas carinatus , Psammodynastes pulverulentus , Pseudoxenodon macrops , Pseudoxyrhopus heterurus , Sibynophis collaris , Stegonotus admiraltiensis , Toxicocalamus goodenoughensis , Trimeresurus albolabris , and Tropidonophis doriae. From these new genome assemblies, we extracted thousands of loci commonly used in systematic and phylogenomic studies on snakes, including target-capture datasets composed of ultraconserved elements (UCEs) and anchored hybrid enriched loci (AHEs), as well as traditional Sanger loci. Phylogenies inferred from the two target-capture loci datasets were identical with each other and strongly congruent with previously published snake phylogenies. To show the additional utility of these non-model genomes for investigative evolutionary research, we mined the genome assemblies of two New Guinea island endemics in our dataset (S. admiraltiensis and T. doriae) for the ATP1a3 gene, a thoroughly researched indicator of resistance to toad toxin ingestion by squamates. We find that both these snakes possess the genotype for toad toxin resistance despite their endemism to New Guinea, a region absent of any toads until the human-mediated introduction of Cane Toads in the 1930s. These species possess identical substitutions that suggest the same bufotoxin resistance as their Australian congenerics (Stegonotus australis and Tropidonophis mairii) which forage on invasive Cane Toads. Herein, we show the utility of short-read high-coverage genomes, as well as improving the deficit of available squamate genomes with associated voucher specimens. [ABSTRACT FROM AUTHOR]

The advent of soft ionization mass spectrometry‐based proteomics in the 1990s led to the development of a new dimension in biology that conceptually allows for the integral analysis of whole proteomes. This transition from a reductionist to a global‐integrative approach is conditioned to the capability of proteomic platforms to generate and analyze complete qualitative and quantitative proteomics data. Paradoxically, the underlying analytical technique, molecular mass spectrometry, is inherently nonquantitative. The turn of the century witnessed the development of analytical strategies to endow proteomics with the ability to quantify proteomes of model organisms in the sense of "an organism for which comprehensive molecular (genomic and/or transcriptomic) resources are available." This essay presents an overview of the strategies and the lights and shadows of the most popular quantification methods highlighting the common misuse of label‐free approaches developed for model species' when applied to quantify the individual components of proteomes of nonmodel species (In this essay we use the term "non‐model" organisms for species lacking comprehensive molecular (genomic and/or transcriptomic) resources, a circumstance that, as we detail in this review‐essay, conditions the quantification of their proteomes.). We also point out the opportunity of combining elemental and molecular mass spectrometry systems into a hybrid instrumental configuration for the parallel identification and absolute quantification of venom proteomes. The successful application of this novel mass spectrometry configuration in snake venomics represents a proof‐of‐concept for a broader and more routine application of hybrid elemental/molecular mass spectrometry setups in other areas of the proteomics field, such as phosphoproteomics, metallomics, and in general in any biological process where a heteroatom (i.e., any atom other than C, H, O, N) forms integral part of its mechanism. [ABSTRACT FROM AUTHOR]

Most bee stings are not life-threatening. Bee venom often causes local, mild allergic reactions in people, but even a single bee sting may induce a fatal anaphylactic reaction. Usually, anaphylactic reaction is the cause of death, but, when a child suffers multiple stings (more than 30), direct toxicity of venom can also be fatal. A three-year-old male child was brought to the hospital with pain, swelling and redness at the sting sites. He had more than 35 stings at various sites over his face, on his tongue and over his body. He died 10 hours after the incidence of the honey bee stings and was maintaining oxygen saturation until the terminal stage of his life. At autopsy, the honey bee sting sites showed redness, swelling and a small effusion of blood surrounding the stinger tracks. On the tongue two stingers were found in situ. Facial puffiness and eyelid swelling, along with congested organs, were also found, but features suggestive of anaphylactic death like airway oedema, mucous plug or cyanosis were absent. Hospital treatment records show that blood pressure remained low with tachycardia despite treatment. Having regard for all the evidence it was concluded that death was due to multiple honey bee stings that caused direct venom toxicity. [ABSTRACT FROM AUTHOR]

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The sole treatment for snakebite envenomation (SBE), the anti-snake venom (ASV), suffers from considerable drawbacks, including side effects and limited species specificity. Additionally, despite its existence for more than a century, uniform availability of good quality ASV does not yet exist. The present review describes the journey of a SBE victim and highlights the global crisis of SBE management. A detailed analysis of the current ASV market has also been presented along with the worldwide snake distribution. The current production of country specific licensed ASV throughout the globe along with their manufacturers has been examined at the snake species level. Furthermore, a detailed analysis of on-ground situation of SBE management in antivenom manufacturing countries has been done using the most recent literature. Additionally, the export and import of different ASVs have been discussed in terms of procurement policies of individual countries, their shortcomings, along with the possible solution at the species level. It is interesting to note that in most countries, the existence of ASV is really either neglected or overstated, implying that it is there but unsuitable for use, or that it is not present but can be obtained from other countries. This highlights the urgent need of significant reassessment and international collaborations not just for development and production, but also for procurement, distribution, availability, and awareness. A PROMISE (Practical ROutes for Managing Indigenous Snakebite Envenoming) approach has also been introduced, offering simple, economical, and easy to adopt steps to efficiently alleviate the worldwide SBE burden. [ABSTRACT FROM AUTHOR]

The yellow scorpion, Buthus boumalenii, has long been recognized as a potentially dangerous species endemic to Morocco. However, there is currently no data on the in vivo toxicity or effects of Buthus boumalenii venom, as it has not been studied to the best of our knowledge. In order to achieve the objective of this study, the LD50 of B. boumalenii venom will be initially calculated, followed by determining its impact on vital organs using histological, biochemical, and behavioral analyses. The investigation also explores potential neurobehavioral impairments in Swiss mice at intervals of 3 hours, 6 hours, and 12 hours post-envenomation. The LD50 for Buthus boumalenii scorpion venom in mice was determined to be 353 µg/kg based on body weight. The findings of the study highlight the potential lethality of B. boumalenii. Observations related to the poisoning provide indications of potential tissue damage in specific vital organs. To sum up, the venom from this scorpion has the potential to result in considerable medical complications, including fatalities, particularly in individuals at risk. Consequently, healthcare practitioners should be knowledgeable about the diverse scorpion species in their regions and adhere to contemporary medical protocols when addressing scorpion envenomation. [ABSTRACT FROM AUTHOR]

Abstract Background The snake genera Atropoides, Cerrophidion, and Metlapilcoatlus form a clade of neotropical pit vipers distributed across Mexico and Central America. This study evaluated the myotoxic and neurotoxic effects of nine species of Atropoides, Cerrophidion, and Metlapilcoatlus, and the neutralising efficacy of the ICP antivenom from Costa Rica against these effects, in the chick biventer cervicis nerve-muscle preparation. Given the prominence of PLA2s within the venom proteomes of these species, we also aimed to determine the neutralising potency of the PLA2 inhibitor, varespladib. Results All venoms showed myotoxic and potential neurotoxic effects, with differential intra-genera and inter-genera potency. This variation was also seen in the antivenom ability to neutralise the muscle damaging pathophysiological effects observed. Variation was also seen in the relative response to the PLA2 inhibitor varespladib. While the myotoxic effects of M. mexicanus and M. nummifer venoms were effectively neutralised by varespladib, indicating myotoxicity is PLA2 mediated, those of C. godmani and M. olmec venoms were not, revealing that the myotoxicity is driven by non-PLA2 toxin types. Conclusions This study characterises the myotoxic and neurotoxic venom activity, as well as neutralisation of venom effects from the Atropoides, Cerrophidion, and Metlapilcoatlus clade of American crotalids. Our findings contribute significant clinical and evolutionary knowledge to a clade of poorly researched snakes. In addition, these results provide a platform for future research into the reciprocal interaction between ecological niche specialisation and venom evolution, as well as highlighting the need to test purified toxins to accurately evaluate the potential effects observed in these venoms.

Nor Osman Sidow,1,2 Abdiwahid Ahmed Ibrahim,1 Nasra Mohamud Hilowle,3 Nasra Ahmed Diblawe,3 Ridwan Mohamud Ali,4 Abdinasir Mohamed Elmi,5 Bakar Ali Adam,1 Mohamed Sheikh Hassan1 1Department of Neurology, Mogadishu-Somalia Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 2Faculty of Medicine and Surgery, Jazeera University, Mogadishu, Somalia; 3Department of Anesthesia and Critical Care, Mogadishu-Somalia Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 4Department of Emergency, Mogadishu-Somalia Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 5Department of Radiology, Mogadishu-Somalia Turkey Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, SomaliaCorrespondence: Abdiwahid Ahmed Ibrahim, Email drabdiwahid00@gmail.comAbstract: Cerebral sinus venous thrombosis (CSVT) is an uncommon and potentially life-threatening neurological disorder that is often missed because its clinical and radiological symptoms are not specific. Snake bites are a rare cause of cerebral venous sinus thrombosis that must be recognized and treated promptly to improve survival. Here, we present a case of a 30-year-old male patient who had cerebral venous thrombosis after snake bite in the rural area of southern Somalia. After close monitoring with anticoagulation, the condition of the patient improved and discharged from the hospital with full of consciousness. There are only a few cases reported in the literature of snake bites causing cerebral venous thrombosis.Keywords: snakebite, cerebral venous thrombosis, venom, viper, anticoagulant