Search Results (527)

The common krait (Bungarus caeruleus) and the endemic Sri Lankan krait (B. ceylonicus) are two species of krait responsible for envenomings in Sri Lanka that result in progressive neuromuscular paralysis. We characterised the in vitro neurotoxicity of B. ceylonicus and B. caeruleus venoms and studied their neutralisation by two commercially available Indian polyvalent antivenoms (i.e., VINS and BHARAT), Thai banded krait antivenom and Australian polyvalent antivenom using the chick biventer cervicis nerve-muscle preparation. Both venoms displayed concentration-dependent neurotoxicity, showing equipotent pre-synaptic neurotoxicity at 0.03 μg/mL. At a higher concentration (1 μg/mL), both venoms showed post-synaptic neurotoxicity, with B. ceylonicus venom being more potent. VINS was unable to neutralise the neurotoxicity of B. ceylonicus venom, but neutralised both pre- and post-synaptic neurotoxicity of B. caeruleus venom. BHARAT neutralised in vitro pre- and post-synaptic activity of both B. ceylonicus and B. caeruleus venoms. Banded krait antivenom and Australian polyvalent antivenoms were unable to fully neutralise the neurotoxicity of either venom at tested concentrations. In conclusion, B. ceylonicus venom shows pre- and post-synaptic neurotoxicity similar to B. caeruleus venom. BHARAT effectively neutralises both pre- and post-synaptic neurotoxicity of B. ceylonicus venom. Both Indian polyvalent antivenoms effectively neutralise neurotoxicity induced by B. caeruleus venom. Full article

Australian elapid snakes possess potent procoagulant venoms, capable of inducing severe venom-induced consumption coagulopathy (VICC) in snakebite victims through rapid activation of the coagulation cascade by converting the FVII and prothrombin zymogens into their active forms. These venoms fall into two mechanistic categories: FXa-only venoms, which hijack host factor Va, and FXa:FVa venoms, containing a complete venom-derived prothrombinase complex. While previous studies have largely focused on human plasma, the ecological and evolutionary drivers behind prey-selective venom efficacy remain understudied. Here, thromboelastography was employed to comparatively evaluate venom coagulotoxicity across prey classes (amphibian, avian, rodent) and human plasma, using a taxonomically diverse selection of Australian snakes. The amphibian-specialist species Pseudechis porphyriacus (Red-Bellied Black Snake) exhibited significantly slower effects on rodent plasma, suggesting evolutionary refinement towards ectothermic prey. In contrast, venoms from dietary generalists retained broad efficacy across all prey types. Intriguingly, notable divergence was observed within Pseudonaja textilis (Eastern Brown Snake): Queensland populations of this species, and all other Pseudonaja (brown snake) species, formed rapid but weak clots in prey and human plasma. However, the South Australian populations of P. textilis produced strong, stable clots across prey plasmas and in human plasma. This is a trait shared with Oxyuranus species (taipans) and therefore represents an evolutionary reversion towards the prothrombinase phenotype present in the Oxyuranus and Pseudonaja last common ancestor. Clinically, this distinction has implications for the pathophysiology of human envenomation, potentially influencing clinical progression, including variations in clinical coagulopathy tests, and antivenom effectiveness. Thus, this study provides critical insight into the ecological selection pressures shaping venom function, highlights intraspecific venom variation linked to geographic and phylogenetic divergence, and underscores the importance of prey-focused research for both evolutionary toxinology and improved clinical management of snakebite. Full article

The World Health Organization (WHO) declared snakebite envenoming (SBE) as a neglected tropical disease in 2017. Antivenom is the gold standard of treatment, but many healthcare barriers exist, and hence, affected populations are often unable to access it. The challenge is further perpetuated by the lack of attention from national health authorities, poor regulatory systems and policies, and mismanagement of antivenom. This study aims to map the evidence regarding snake antivenom regulations globally and identify gaps in the literature to inform future research and policy. This review was conducted using the original Arksey and O’Malley framework by three independent reviewers, and the results were reported using the Preferred Reporting Items for Systematic reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). A search strategy was developed with assistance from a librarian, and six databases were searched: PubMed, SCOPUS, ProQuest Central, Africa Wide Web, Academic Search Output, and Web of Science. Screening was conducted independently by the reviewers, using Rayyan, and conflicts were resolved with discussions. A total of 84 articles were included for data extraction. The major themes that emerged from the included studies were regarding antivenom availability, accessibility, manufacturing, and regulations. The study revealed massive gaps in terms of policies governing antivenom management, especially in Asia and Africa. The literature does not offer sufficient evidence on management guidelines for antivenom in the endemic regions, despite identifying the challenges in supply. However, significant information from Latin America revealed self-sufficient production, involvement of national health bodies in establishing efficient regulations, effective distribution nationally and regionally, and technology sharing to reduce SBE-related mortality. Full article

In Brazil, the annual scorpion sting cases surpass those of other neglected tropical diseases, highlighting a significant public health issue. The severity of scorpion envenomation relates to the venom’s rapid action, complex composition, species identification challenges, and limited antivenom availability. This work aimed to characterize the venom of Tityus confluens through proteomic, enzymatic, and biological analyses while also assessing its reactivity to anti-scorpion antivenom. The electrophoretic analysis revealed seven protein bands, with the most prominent bands at 30, 15, and 10 kDa. The C18-RP-HPLC analysis isolated sixteen primary fractions. The proteomic analysis identified various toxins, including potassium channel toxins, sodium channel toxins, and antimicrobial peptides, as well as other proteins such as hypotensin and metalloproteinases. Antigenic components were identified in the T. confluens venom, which displayed dose-dependent but time-independent amylolytic activity. The ATPase activity significantly increased with 1–10 μg of venom. No cytotoxic effects were observed on carcinoma or non-tumoral cell lines. The T. confluens venom features a complex protein composition rich in toxins that target ion channels and enzymes. It exhibits active enzymatic and antigenic properties, and displays low cytotoxicity. This is the first proteomic research on the composition of T. confluens venom and may provide valuable insights into understanding the clinical manifestations of scorpion stings. Full article

A review was conducted on snakebites in Central America. Information was extracted using the databases of PubMed, SciELO, and LILACS. Information included retrospective studies, case reports, and case series; in this way, valuable information was retrieved from limited sources. The identified studies comprised those discussing envenoming snakebites. Several species were identified, but three of them had major epidemiological features impacting envenoming by snakebites: Bothrops asper, Crotalus simus, and Micrurus sp. Adolescents and young adult males living in rural areas and engaged in agricultural activities were identified as the main victims of snakebites by clinical records. Symptoms of local damage in the bite sites included edema and skin and muscle necrosis. In addition, the cardiovascular system was affected, with symptoms like hypotension, bleeding, and coagulation disorders. Neurotoxicity causing sensitivity and motricity problems was also reported. For El Salvador, accidents caused by Crotalus simus and Micrurus spp. were given more attention due to their greater relevance. The role of Bothrops species was more relevant in the envenoming reported by other countries. Treatment was found to be provided based on antivenoms produced in Costa Rica, and the recovery of the patients depended on the time elapsed between the accident and the initial treatment in the healthcare system. Full article

Differences in venom within snake species can affect the efficacy of antivenom, but how this variation manifests across broad geographical scales remains poorly understood. Naja atra envenoming causes severe morbidity in China, yet whether intraspecific venom variation exists across mainland regions is unknown. We collected venom samples from seven biogeographical regions (spanning > 2000 km latitude). Venom lethality, systemic toxicity (organ damage biomarkers and coagulopathy), and histopathology of major organs were assessed. Neutralization by antivenom and label-free quantitative proteomics (LC-MS/MS) were also performed. The results revealed a non-uniform LD₅₀, with venom from Yunnan exhibiting the highest lethality (2.1-fold higher than venom from Zhejiang, p < 0.001). Commercial antivenom showed lower neutralization efficacy against the venom from the Yunnan, Guangxi, and Guangdong regions. Regarding organ damage and coagulopathy, venom from Yunnan caused severe liver damage, while venom from the Zhejiang region induced significant coagulopathy. Finally, proteomic profiles identified 175 proteins: venom from Yunnan was dominated by phospholipases, contrasting with eastern regions (Anhui/Zhejiang: cytotoxins CTXs > 30%). Venom from Guangdong contained higher levels of the weak neurotoxin NNAM2 (5.2%). Collectively, significant geographical divergence exists in Chinese Cobra venom composition, systemic toxicity, and antivenom susceptibility, driven by differential expression of key toxins. Our study provides a molecular basis for precision management of snakebites, and we call for optimized antivenom production tailored to regional variations. Full article

Background/Objectives: Most snakebite incidents in Latin America are caused by species of the Bothrops genus. Their venom induces severe local effects, against which antivenom therapy has limited efficacy. Metabolites derived from Coffea arabica have demonstrated anti-inflammatory and anticoagulant properties, suggesting their potential as therapeutic agents to inhibit the local effects induced by B. asper venom. Methods: Three enzymatic assays were performed: inhibition of the procoagulant and amidolytic activities of snake venom serine proteinases (SVSPs); inhibition of the proteolytic activity of snake venom metalloproteinases (SVMPs); and inhibition of the catalytic activity of snake venom phospholipases A₂ (PLA_2s). Additionally, molecular docking studies were conducted to propose potential inhibitory mechanisms of the metabolites chlorogenic acid, caffeine, and caffeic acid. Results: Green and roasted coffee extracts partially inhibited the enzymatic activity of SVSPs and SVMPs. Notably, the green coffee extract, at a 1:20 ratio, effectively inhibited PLA₂ activity. Among the individual metabolites tested, partial inhibition of SVSP and PLA₂ activities was observed, whereas no significant inhibition of SVMP proteolytic activity was detected. Chlorogenic acid was the most effective metabolite, significantly prolonging plasma coagulation time and achieving up to 82% inhibition at a concentration of 62.5 μM. Molecular docking analysis revealed interactions between chlorogenic acid and key active site residues of SVSP and PLA₂ enzymes from B. asper venom. Conclusions: The roasted coffee extract demonstrated the highest inhibitory effect on venom toxins, potentially due to the formation of bioactive compounds during the Maillard reaction. Molecular modeling suggests that the tested inhibitors may bind to and occupy the substrate-binding clefts of the target enzymes. These findings support further in vivo research to explore the use of plant-derived polyphenols as adjuvant therapies in the treatment of snakebite envenoming. Full article

Phospholipase A1 (Ves a 1), a major toxin from Vespa affinis venom, poses significant risks to allergic individuals. Nevertheless, the epitope determinants of Ves a 1 have not been characterized. Thus, identifying its linear B-cell epitopes is crucial for understanding envenomation mechanisms. In this study, we predicted and identified B-cell epitopes EP5 and EP6 as potential candidates. EP5 formed an α-helix at the active site of Ves a 1, whereas EP6 adopted an extended loop conformation. Both synthetic peptides were synthesized and evaluated for their inhibitory effects using immune-inhibitory assays with polyclonal antibodies (pAbs) targeting both native (nVes a 1) and recombinant (rVes a 1) forms. The Ves a 1 polyclonal antibodies (pAb-nVes a 1 and pAb-Ves a 1) were produced, and their specificity binding to Ves a 1 was confirmed by Western blot. Next, ELISA inhibition assays showed that EP5 and EP6 significantly blocked pAb binding to both nVes a 1 and rVes a 1. Dot blot and Western blot assays supported these findings, particularly with stronger inhibition toward rVes a 1. Furthermore, enzymatic assays indicated that nVes a 1 and rVes a 1 retained phospholipase activity. Immunoinformatics docking showed that EP5 and EP6 specifically bind to a single-chain variable fragment antibody (scFv) targeting Naja naja PLA2. Molecular analysis revealed similar amino acid interactions to the template, suggesting effective paratope–epitope binding. These results support the potential of EP5 and EP6 for future diagnosis and therapy of V. affinis venom allergy. Full article

The snakes from the genus Bothrops are responsible for most of the ophidic accidents in Brazil, and Bothrops atrox represents one of these species. Envenomation by these snakes results in systemic effects and is often associated with early mortality following snakebite incidents. The present study investigates the pharmacological properties of Bothrops atrox venom (VBA), focusing specifically on its impact on renal blood flow. Following the renal perfusion procedure, kidney tissues were processed for histopathological examination. Statistical analysis of all evaluated parameters was conducted using ANOVA and Student’s t-test, with significance set at p < 0.005. Administration of VBA resulted in a marked reduction in both perfusion pressure and renal vascular resistance. In contrast, there was a significant elevation in urinary output and glomerular filtration rate. Histological changes observed in the perfused kidneys were mild. The involvement of nitric oxide in the pressor effects of Bothrops atrox venom was not investigated in renal perfusion systems or in in vivo models. Treatment with VBA led to elevated nitrite levels in the bloodstream of the experimental animals. This effect was completely inhibited following pharmacological blockade with L-NAME. Based on these findings, we conclude that VBA alters renal function and promotes increased nitric oxide production. Full article

Snakebite remains the most neglected tropical disease globally, with India experiencing the highest rates of mortality and morbidity. While most envenomation cases in India are attributed to the ‘big four’ snakes, research has predominantly focused on Russell’s viper (Daboia russelii), spectacled cobra (Naja naja), and common krait (Bungarus caeruleus), leading to a considerable gap in our understanding of saw-scaled viper (Echis carinatus carinatus) venoms. For instance, the venom gland transcriptome and inter- and intra-population venom variation in E. c. carinatus have largely remained uninvestigated. A single study to date has assessed the effectiveness of commercial antivenoms against this species under in vivo conditions. To address these crucial knowledge gaps, we conducted a detailed investigation of E. c. carinatus venom and reported the first venom gland transcriptome. A proteotranscriptomic evaluation revealed snake venom metalloproteinases, C-type lectins, L-amino acid oxidases, phospholipase A₂s, and snake venom serine proteases as the major toxins. Moreover, we assessed the intra-population venom variation in this species using an array of biochemical analyses. Finally, we determined the venom toxicity and the neutralising efficacy of a commercial antivenom using a murine model of snake envenoming. Our results provide a thorough molecular and functional profile of E. c. carinatus venom. Full article

The composition of Australian snake venoms is the least well-known of any continent. We characterised the venom proteome of the southern death adder Acanthophis antarcticus—one of the world’s most morphologically and ecologically divergent elapids. Using a combined bottom-up proteomic and venom gland transcriptomic approach employing reverse-phase chromatographic and gel electrophoretic fractionation strategies in the bottom-up proteomic workflow, we characterised 92.8% of the venom, comprising twelve different toxin identification hits belonging to seven toxin families. The most abundant protein family was three-finger toxins (3FTxs; 59.8% whole venom), consisting mostly of one long-chain neurotoxin, alpha-elapitoxin-Aa2b making up 59% of the venom and two proteoforms of another long-chain neurotoxin. Phospholipase A₂s (PLA₂s) were the second most abundant, with four different toxins making up 22.5% of the venom. One toxin was similar to two previous non-neurotoxic PLA₂s, making up 16% of the venom. The remaining protein families present were CTL (3.6%), NGF (2.5%), CRiSP (1.8%), LAAO (1.4%), and AChE (0.8%). A. antarcticus is the first Australian elapid characterised that has a 3FTx dominant venom, a composition typical of elapids on other continents, particularly cobras Naja sp. The fact that A. antarcticus has a venom composition similar to cobra venom while having a viper-like ecology illustrates that similar venom expressions can evolve independently of ecology. The predominance of post-synaptic neurotoxins (3FTxs) and pre-synaptic neurotoxins (PLA₂) is consistent with the neurotoxic clinical effects of envenomation in humans. Full article

Background: Snake envenomation is a major public health issue in Nigeria, primarily due to bites from Echis ocellatus, Naja nigricollis, and Bitis arietans. Understanding their venom composition is essential for effective antivenom development. This study characterizes and compares the venom proteomes of these snakes using iTRAQ-based proteomics, focusing on key toxin families and their relative abundances. Methods: Venom samples were ethically collected from adult snakes, pooled by species, lyophilized, and stored for proteomic analysis. Proteins were extracted, digested with trypsin, and labeled with iTRAQ. Peptides were analyzed via mass spectrometry, and data were processed using Mascot and IQuant for protein identification and quantification. Results: E. ocellatus and B. arietans venoms had similar profiles, rich in C-type lectins, serine proteases, and phospholipase A₂s. These comprised 17%, 11%, and 5% in E. ocellatus and 47%, 10%, and 7% in B. arietans, with metalloproteinases dominating both (53% and 47%). In N. nigricollis, three-finger toxins (9%) were most abundant, followed by metalloproteinases (3%). All species shared four core protein families, with N. nigricollis also containing four uncharacterized proteins. Conclusions: This study highlights venom compositional differences, advancing snake venom biology and informing targeted antivenom development. Full article

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The puff adder (Bitis arietans) and saw-scaled viper (Echis romani) have cytotoxic venoms that cause permanent injury via dermonecrosis around the bite site. Identifying the cytotoxic toxins within these venoms will allow for the development of targeted treatments to prevent snakebite morbidity. In this study, venoms from both species were fractionated using gel filtration chromatography, and a combination of cytotoxicity approaches, SDS-PAGE gel electrophoresis, and enzymatic assays were applied to identify the venom cytotoxins in the resulting fractions. Our results indicate that snake venom metalloproteinase (SVMP) toxins are responsible for causing cytotoxic effects across both venoms. The PI subclass of SVMPs is likely the main driver of cytotoxicity following envenoming by B. arietans, while the structurally distinct PIII subclass of SVMPs is mostly responsible for conveying this effect in E. romani venom. Identifying distinct SVMPs as cytotoxicity-causing toxins in these two African viper venoms will facilitate the future design and development of novel therapeutics targeting these medically important venoms, which in turn could help to mitigate the severe life- and limb-threatening consequences of tropical snakebites. Full article

Scorpion envenomation is a public health issue in tropical and subtropical regions. Currently, there is limited data on the biological effects of Hottentotta judaicus scorpion venom (HjSV) in mammals. This study aims to analyze the effect of HjSV on lipopolysaccharide (LPS)-induced hyperalgesia in mice and its potential modulation of the immunological inflammatory response. Hyperalgesia is characterized by an increased response to pain, accompanied by heightened sensitivity that ranges from mild discomfort to intense pain. A series of tests were conducted, including heat resistance testing in BALB/c mice injected subcutaneously with LPS to induce hyperalgesia and intraperitoneally with HjSV. The hot plate test, used to assess pain endurance in mice, showed that LPS-injected mice, particularly females, exhibited heightened pain sensitivity. This suggests possible sex-based differences in pain perception. When HjSV was administered alone, a reduction in pain sensitivity was observed in both sexes. Additionally, ELISA tests were performed to assess changes in the secretion of inflammatory cytokines IL-4, IL-10, IL-6, IFN-γ, and TNF-α. A consistent increase in both pro- and anti-inflammatory cytokines was observed at early time points in females injected with HjSV alone. Moreover, the hyperalgesia induced by LPS was significantly reduced when HjSV was co-administered, indicating an anti-inflammatory effect at early stages. These findings suggest that HjSV has a significant immunomodulatory effect, potentially exerting anti-inflammatory action during acute inflammation. This effect appears to be time-dependent, diminishing as the immune response transitions toward its adaptive phase. Full article

Strophanthus sarmentosus is recognised for various ethnomedicinal applications, including treatment after snakebites. However, only limited scientific evidence exists on its antivenomous capabilities. This study investigates the efficacy of methanol and ethylacetate extracts from S. sarmentosus leaves and roots against Echis ocellatus venom. A non-toxic range for the extracts was determined in rats, and assays were performed to test their anti-hemorrhagic and anti-hemolytic activity as well as their influence on venom-induced blood clotting. In all of these experiments, the extracts demonstrated significant positive effects equal to or better than antivenom. Moreover, the extracts strongly inhibited and even abolished the digestion of the vasoactive neuropeptide bradykinin by snake venom metalloproteinases. Strophantus plants are known for their high content of cardiac glycosides, one of which is the commercially available ouabain, that by itself also considerably inhibited venom-induced bradykinin cleavage. Although ouabain is only present in low amounts in S. sarmentosus when compared to other cardenolides of similar structure, it can be hypothesized that members of this substance class may also have inhibitory properties against venom proteases. S. sarmentosus additionally contains bioactive substances such as flavonoids, terpenoids, tannins, saponins, and alkaloids, which contribute to its protective effects. The study provides scientific data to explain the success of the traditional use of S. sarmentosus plant extracts as a first aid against envenomation in rural Africa. Full article