Search Results (51)

Background/Objectives: Snakebite envenoming remains a critical yet frequently under-recognized cause of mortality in many parts of the world, particularly in tropical and rural areas where access to timely medical care and accurate post-mortem investigation is limited. While clinical and epidemiological data on snakebites have been extensively studied, the forensic characterization of fatal envenomations remains fragmentary and inconsistently documented. This review aims to synthesize the existing literature on autopsy-confirmed snakebite deaths, focusing on the pathological and toxicological evidence that supports cause-of-death determinations in forensic settings. Methods: A comprehensive search of the PubMed NCBI databases identified nine relevant studies, including case reports, retrospective analyses, and systematic reviews. Results: Across these reports, a range of lethal mechanisms were identified, including venom-induced consumption coagulopathy (VICC), acute renal failure (frequently in the setting of rhabdomyolysis and acute tubular necrosis), neurotoxic respiratory arrest, multi-organ necrosis, and myocardial infarction. Histological findings frequently revealed glomerular and tubular necrosis, pulmonary edema and/or hemorrhage, pituitary and adrenal hemorrhage, and cerebral ischemic changes. Toxicological confirmation was achieved in several cases using ELISA and liquid chromatography–mass spectrometry (LC–MS/MS), underscoring the importance of biochemical validation in post-mortem diagnosis and the value of analytical tools beyond ELISA (e.g., immunoaffinity LC–MS/MS, venom-specific immunohistochemistry, zymography for SVMP activity). Conclusions: Our findings highlight the variability in venom effects across snake families—particularly Viperidae, Elapidae, and Lamprophiidae/Atractaspididae—and emphasize the indispensable role of forensic autopsy in distinguishing snakebite envenoming from other causes of sudden or unexplained death. However, significant limitations persist, including inconsistent autopsy protocols, lack of species-specific venom assays, and poor integration of toxicological methods in routine forensic practice. Addressing these gaps through standardized forensic guidelines and improved access to diagnostic tools is essential for enhancing the accuracy of death investigations in envenoming-endemic regions. Full article

Acanthophis antarcticus, commonly known as the death adder, is a venomous Australian snake and a member of the Elapidae family. Due to its robust body and triangular head, it was historically misclassified as a viper. Its venom is known for neurotoxic, hemorrhagic, and hemolytic effects but displays low anticoagulant activity. Although key toxins such as three-finger toxins (3FTxs) and phospholipase A₂ (PLA₂) have been previously described, no study has integrated proteomic and functional analyses to date. In this study, we conducted a comprehensive characterization of A. antarcticus venom. Reverse-phase high-performance liquid chromatography (RP-HPLC) followed by LC-MS/MS enabled the identification of nine toxin families, with 3FTxs and PLA₂ as the most abundant. Less abundant but functionally relevant toxins included Kunitz-type inhibitors, CRISP, SVMP, LAAO, NGF, natriuretic peptides, and nucleotidases, the latter being reported here for the first time based on proteomic evidence. Hydrophilic interaction chromatography (HILIC) coupled with MALDI-TOF was used to analyze polar, non-retained venom components, revealing the presence of low-molecular-weight peptides (2–4 kDa). Functional assays confirmed the enzymatic activity of HYAL, PLA₂, and LAAO and, for the first time, demonstrated inhibitory activity on serine peptidases and fibrinogenolytic activity in the venom of this species. These findings expand our understanding of the biochemical and functional diversity of this venom. 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

Snakebite envenoming constitutes a significant global health issue, particularly in Africa, where venomous species such as Echis vipers and Dendroaspis mambas pose substantial risks to human health. This study employs a standardized venomics workflow to comprehensively characterize and comparatively quantify the venom composition of nine medically relevant snake species chosen from among the deadliest in Africa. Utilizing shotgun venom proteomics and venom gland transcriptomics, we report detailed profiles of venom complexity, highlighting the relative abundance of dominant toxin families such as three-finger toxins and Kunitz-type proteins in Dendroaspis, and metalloproteinases and phospholipases A₂ in Echis. We delineate here the relative abundance and structural diversity of venom components. Key to our proteomic approach is the implementation of Multi-Enzymatic Limited Digestion (MELD), which improved protein sequence coverage and enabled the identification of rare toxin families such as hyaluronidases and renin-like proteases, by multiplying the overlap of generated peptides and enhancing the characterization of both toxin and non-toxin components within the venoms. The culmination of these efforts resulted in the construction of a detailed toxin database, providing insights into the biological roles and potential therapeutic targets of venom proteins and peptides. The findings here compellingly validate the MELD technique, reinforcing its reproducibility as a valuable characterization approach applied to venomics. This research significantly advances our understanding of venom complexity in African snake species, including representatives of both Viperidae and Elapidae families. By elucidating venom composition and toxin profiles, our study paves the way for the development of targeted therapies aimed at mitigating the morbidity and mortality associated with snakebite envenoming globally. Full article

Snakes are stimuli inducing an ancestral fear response in humans and other primates. Certain snakes evoke more subjective fear than others. True vipers are high-fear-eliciting snakes for both African and European respondents. This can be explained by the evolutionary experience of human ancestors in Africa. The question arises as to how snakes living in the Americas and Australia, with which humans have no evolutionary experience, will be evaluated. While these snakes belong to broader taxonomic groups that have distant relatives in the Old World, they have evolved independently for tens of millions of years. We prepared a set of 32 pictures depicting eight American pit vipers, eight Australian elapids, eight constrictors, and eight colubrids and asked the respondents to rank these stimuli according to the fear these snakes evoke. Here, we show a high cross-cultural agreement between evaluations by African and European respondents. Snakes characterized by a robust body shape, such as American pit vipers, Australian death adders, pythons, and boas, were the most fear-evoking. The body width was the strongest predictor of evoked fear. The contribution of coloration and pattern of the stimulus to the fear response was not proved. This supports the view that the patterns of fear are not dependent on direct experience, but its underlying mechanisms are shared cross-culturally. Full article

Functional characterization of peptide fraction (PF) from snake venom has provided novel opportunities to investigate possible neuroprotective compounds relevant to pharmaceuticals. This study was performed to investigate the PF-mediated neuroprotection obtained from Naja mandalayensis snake venom, a member of the Elapidae family, using two neuronal cell lines, undifferentiated PC12 and differentiated mHippoE-18, in response to H₂O₂-induced oxidative stress. Cells were pre-treated for 4 h with PF (10, 1, 0.01, and 0.001 μg mL⁻¹), and thereafter exposed to H₂O₂ (0.5 mmol L⁻¹) for 20 h. Then, the oxidative stress markers and label-free differential proteome strategy were analyzed to understand the neuroprotective effects of PF. In PC12 cells, PF showed no neuroprotective effects against oxidative stress. In mHippoE-18 cells, PF at 0.01 and 0.001 μg mL⁻¹ increased the viability and metabolism of cells against H₂O₂-induced neurotoxicity, reducing reactive oxygen species (ROS) generation. Interestingly, PF also exhibited a substantial reduction in baseline ROS levels compared to the control, indicating that PF could have compounds with antioxidant features. The comparative proteomic profiling identified 53 proteins with differential expression related to antioxidant action, catalysis, molecular function regulators, structural molecule activity, translation regulatory activity, ATP, and binding. The PF + H₂O₂ group indicated that protein expression is 6% upregulated, 4% downregulated, and 94% unchanged compared to the H₂O₂ group. Three significant proteins upregulated in the PF + H₂O₂ group, including elongation factor 2 (P58252), proteasome subunit alpha type (E9Q0X0), and E2 ubiquitin-conjugating enzyme (A0A338P786), suggested that PF-mediated neuroprotection happens through translational regulation and the degradation of defective proteins via the proteasome complex. Additionally, differential protein expression in PF changed the metabolism, protein synthesis, synaptic activity, and intracellular transport, suggesting that PF contains the rich mixture of bioactive peptides of interest pharmacologically. Overall, this study offers new opportunities for evaluating whether PF’s neuroprotective features in specific neuronal cells are maintained and to investigate neurodegenerative disease drug development processes. Full article

Kraits are venomous snakes of the genus Bungarus from the family Elapidae. Their venom typically demonstrates neurotoxicity; however, the toxicity is significantly influenced by the snake’s species and geographical origin. Among the Bungarus species, Bungarus suzhenae and B. bungaroides have been poorly studied, with little to no information available regarding their venom composition. In this study, a proteomic approach was employed using LC-MS/MS to identify proteins from trypsin-digested peptides. The analysis revealed 102 venom-related proteins from 18 distinct functional protein families in the venom of B. suzhenae, with the primary components being three-finger toxins (3-FTx, 25.84%), phospholipase A₂ (PLA₂, 40.29%), L-amino acid oxidase (LAAO, 10.33%), Kunitz-type serine protease inhibitors (KUN, 9.48%), and snake venom metalloproteinases (SVMPs, 6.13%). In the venom of B. bungaroides, 99 proteins from 17 families were identified, with primary components being 3-FTx (33.87%), PLA₂ (37.91%), LAAO (4.21%), and KUN (16.60%). Enzymatic activity assays confirmed the presence of key venom enzymes. Additionally, the LD50 values for B. suzhenae and B. bungaroides were 0.0133 μg/g and 0.752 μg/g, respectively, providing a reference for toxicity studies of these two species. This research elucidates the proteomic differences in the venoms of these two species, offering a foundation for developing antivenoms and clinical treatments for envenomation. Full article

“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. Full article

Viruses in the subfamily Serpentovirinae (order Nidovirales, family Tobaniviridae) can cause significant morbidity and mortality in captive snakes, but documented infections have been limited to snakes of the Boidae, Colubridae, Homalopsidae, and Pythonidae families. Infections can either be subclinical or associated with oral and/or respiratory disease. Beginning in June 2019, a population of over 150 confiscated snakes was screened for serpentovirus as part of a quarantine disease investigation. Antemortem oropharyngeal swabs or lung tissue collected postmortem were screened for serpentovirus by PCR, and 92/165 (56.0%) of snakes tested were positive for serpentovirus. Serpentoviruses were detected in fourteen species of Viperidae native to Asia, Africa, and South America and a single species of Elapidae native to Australia. When present, clinical signs included thin body condition, abnormal behavior or breathing, stomatitis, and/or mortality. Postmortem findings included variably severe inflammation, necrosis, and/or epithelial proliferation throughout the respiratory and upper gastrointestinal tracts. Genetic characterization of the detected serpentoviruses identified four unique viral clades phylogenetically distinct from recognized serpentovirus genera. Pairwise uncorrected distance analysis supported the phylogenetic analysis and indicated that the viper serpentoviruses likely represent the first members of a novel genus in the subfamily Serpentovirinae. The reported findings represent the first documentation of serpentoviruses in venomous snakes (Viperidae and Elapidae), greatly expanding the susceptible host range for these viruses and highlighting the importance of serpentovirus screening in all captive snake populations. Full article

Kunitz-type peptide expression has been described in the venom of snakes of the Viperidae, Elapidae and Colubridae families. This work aimed to identify these peptides in the venom gland transcriptome of the coral snake Micrurus mipartitus. Transcriptomic analysis revealed a high diversity of venom-associated Kunitz serine protease inhibitor proteins (KSPIs). A total of eight copies of KSPIs were predicted and grouped into four distinctive types, including short KSPI, long KSPI, Kunitz–Waprin (Ku-WAP) proteins, and a multi-domain Kunitz-type protein. From these, one short KSPI showed high identity with Micrurus tener and Austrelaps superbus. The long KSPI group exhibited similarity within the Micrurus genus and showed homology with various elapid snakes and even with the colubrid Pantherophis guttatus. A third group suggested the presence of Kunitz domains in addition to a whey-acidic-protein-type four-disulfide core domain. Finally, the fourth group corresponded to a transcript copy with a putative 511 amino acid protein, formerly annotated as KSPI, which UniProt classified as SPINT1. In conclusion, this study showed the diversity of Kunitz-type proteins expressed in the venom gland transcriptome of M. mipartitus. Full article

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is still very limited when compared to that of other Elapidae snakes like cobras, kraits, and mambas. In this study, two previously described 3FTx from the venom of M. corallinus, NXH1 (3SOC1_MICCO), and NXH8 (3NO48_MICCO) were characterized. Using in silico, in vitro, and ex vivo experiments, the biological activities of these toxins were predicted and evaluated. The results showed that only NXH8 was capable of binding to skeletal muscle cells and modulating the activity of nAChRs in nerve–diaphragm preparations. These effects were antagonized by anti-rNXH8 or antielapidic sera. Sequence analysis revealed that the NXH1 toxin possesses eight cysteine residues and four disulfide bonds, while the NXH8 toxin has a primary structure similar to that of non-conventional 3FTx, with an additional disulfide bond on the first loop. These findings add more information related to the structural diversity present within the 3FTx class, while expanding our understanding of the mechanisms of the toxicity of this coralsnake venom and opening new perspectives for developing more effective therapeutic interventions. Full article

Snakes contain three types of phospholipase A₂ (PLA₂)-inhibitory proteins in their blood, PLIα, β, and γ, which protect them from their own venom, PLA₂. PLIβ is the snake ortholog of leucine-rich α₂ glycoprotein (LRG). Since autologous cytochrome c (Cyt c) serves as an endogenous ligand for LRG, in this study, we purified snake LRGs from various snake serum samples using Cyt c affinity chromatography. All purified snake LRGs were found to be dimers linked by disulfide bonds. Laticauda semifasciata and Naja kaouthia LRGs showed no inhibitory activity against L. semifasciata PLA₂ and weak inhibitory activity against Gloydius brevicauda basic PLA₂. Elaphe climacophora PLIβ had weaker inhibitory activity against G. brevicauda basic PLA₂ than G. brevicauda and Elaphe quadrivirgata PLIs, which are abundant in blood and known to neutralize G. brevicauda basic PLA₂. Protobothrops flavoviridis LRG showed no inhibitory activity against basic venom PLA₂, PL-X, or G. brevicauda basic PLA₂. Binding analysis of P. flavoviridis LRG using surface plasmon resonance showed very strong binding to snake Cyt c, followed by that to horse Cyt c, weak binding to yeast Cyt c, and no binding to P. flavoviridis PL-X or BPI/II. We also deduced the amino acid sequences of L. semifasciata and P. flavoviridis LRG by means of cDNA sequencing and compared them with those of other known sequences of PLIs and LRGs. This study concluded that snake LRG can potentially inhibit basic PLA₂, but, whether it actually functions as a PLA₂-inhibitory protein, PLIβ, depends on the snake. Full article

Colombia encompasses three mountain ranges that divide the country into five natural regions: Andes, Pacific, Caribbean, Amazon, and Orinoquia. These regions offer an impressive range of climates, altitudes, and landscapes, which lead to a high snake biodiversity. Of the almost 300 snake species reported in Colombia, nearly 50 are categorized as venomous. This high diversity of species contrasts with the small number of studies to characterize their venom compositions and natural history in the different ecoregions. This work reviews the available information about the venom composition, isolated toxins, and potential applications of snake species found in Colombia. Data compilation was conducted according to the PRISMA guidelines, and the systematic literature search was carried out in Pubmed/MEDLINE. Venom proteomes from nine Viperidae and three Elapidae species have been described using quantitative analytical strategies. In addition, venoms of three Colubridae species have been studied. Bioactivities reported for some of the venoms or isolated components—such as antibacterial, cytotoxicity on tumoral cell lines, and antiplasmodial properties—may be of interest to develop potential applications. Overall, this review indicates that, despite recent progress in the characterization of venoms from several Colombian snakes, it is necessary to perform further studies on the many species whose venoms remain essentially unexplored, especially those of the poorly known genus Micrurus. Full article

Snake venom research has historically focused on front-fanged species (Viperidae and Elapidae), limiting our knowledge of venom evolution in rear-fanged snakes across their ecologically diverse phylogeny. Three-finger toxins (3FTxs) are a known neurotoxic component in the venoms of some rear-fanged snakes (Colubridae: Colubrinae), but it is unclear how prevalent 3FTxs are both in expression within venom glands and more broadly among colubrine species. Here, we used a transcriptomic approach to characterize the venom expression profiles of four species of colubrine snakes from the Neotropics that were dominated by 3FTx expression (in the genera Chironius, Oxybelis, Rhinobothryum, and Spilotes). By reconstructing the gene trees of 3FTxs, we found evidence of putative novel heterodimers in the sequences of Chironius multiventris and Oxybelis aeneus, revealing an instance of parallel evolution of this structural change in 3FTxs among rear-fanged colubrine snakes. We also found positive selection at sites within structural loops or “fingers” of 3FTxs, indicating these areas may be key binding sites that interact with prey target molecules. Overall, our results highlight the importance of exploring the venoms of understudied species in reconstructing the full evolutionary history of toxins across the tree of life. Full article

The distribution and relative potency of post-synaptic neurotoxic activity within Crotalinae venoms has been the subject of less investigation in comparison with Elapidae snake venoms. No previous studies have investigated post-synaptic neurotoxic activity within the Atropoides, Metlapilcoatlus, Cerrophidion, and Porthidium clade. Given the specificity of neurotoxins to relevant prey types, we aimed to uncover any activity present within this clade of snakes that may have been overlooked due to lower potency upon humans and thus not appearing as a clinical feature. Using biolayer interferometry, we assessed the relative binding of crude venoms to amphibian, lizard, bird, rodent and human α-1 nAChR orthosteric sites. We report potent alpha-1 orthosteric site binding in venoms from Atropoides picadoi, Metlapilcoatlus occiduus, M. olmec, M. mexicanus, M. nummifer. Lower levels of binding, but still notable, were evident for Cerrophidion godmani, C. tzotzilorum and C. wilsoni venoms. No activity was observed for Porthidium venoms, which is consistent with significant alpha-1 orthosteric site neurotoxicity being a trait that was amplified in the last common ancestor of Atropoides/Cerrophidion/Metlapilcoatlus subsequent to the split by Porthidium. We also observed potent taxon-selective activity, with strong selection for non-mammalian targets (amphibian, lizard, and bird). As these are poorly studied snakes, much of what is known about them is from clinical reports. The lack of affinity towards mammalian targets may explain the knowledge gap in neurotoxic activity within these species, since symptoms would not appear in bite reports. This study reports novel venom activity, which was previously unreported, indicating toxins that bind to post-synaptic receptors may be more widespread in pit vipers than previously considered. While these effects appear to not be clinically significant due to lineage-specific effects, they are of significant evolutionary novelty and of biodiscovery interest. This work sets the stage for future research directions, such as the use of in vitro and in vivo models to determine whether the alpha-1 orthosteric site binding observed within this study confers neurotoxic venom activity. Full article