Search Results (746)

Snakebite envenoming is a major yet neglected tropical disease in sub-Saharan Africa, where antivenom efficacy is critically limited by intraspecific venom variation shaped by local ecological pressures. Nigeria’s sharply contrasting Sudan Savanna (North) and Lowland Rainforest (South) provide an ideal natural system to investigate this variation, yet a comparative analysis of its medically important snakes has been lacking. We conducted an integrated proteomic and functional characterization of venoms from the puff adder (Bitis arietans) and black-necked spitting cobra (Naja nigricollis) collected in Kaduna (North) and Ibadan (South). Using high-resolution LC-MS/MS, SDS-PAGE, and biochemical assays (phospholipase A₂, protease, fibrinogenolytic, hemolytic, and coagulation activities), we mapped region-specific venom compositions and characterized their functional activities. Bitis arietans displayed region-associated divergence: southern venom was enriched in serine proteases, whereas northern venom was dominated by lectins and distinct snake venom metalloproteinase isoforms. Naja nigricollis showed a conserved phospholipase A₂/three-finger toxins backbone, yet southern venoms exhibited elevated snake venom metalloproteinase III and L-amino acid oxidase. These molecular differences manifested functionally, with southern B. arietans venom showing higher protease activity than northern B. arietans, whereas southern and northern N. nigricollis venom exhibited similar protease activity but enhanced phospholipase A₂ activity in southern N. nigricollis. This work provides the first integrated proteomic and functional comparison of venoms from northern and southern Nigerian venom sample of B. arietans and N. nigricollis. While based on a limited number of individuals, the observed differences should be considered preliminary and indicative of potential regional trends rather than population-level characteristics. Full article

The Cape cobra (Naja nivea), one of Africa’s most lethal snakes, can cause rapid, life-threatening paralysis. However, the impact of this venom on platelet function and blood coagulation remains poorly understood. To address this gap, we investigated the enzymatic profiles and the impacts of N. nivea venom on multiple aspects of haemostasis using human whole blood. Our results illustrate that Cape cobra venom significantly increases clotting time in rotational thromboelastometry without affecting other coagulation parameters. This venom significantly inhibits platelet aggregation and activation yet does not exert cytotoxic effects on platelets. The venom was subsequently fractionated using reverse-phase high-performance liquid chromatography, and the most potent purified fraction was identified as a cytotoxin (three-finger toxin) through mass spectrometry. This purified fraction showed an inhibitory effect on platelet activity. These findings highlight that N. nivea venom can induce haemotoxicity in addition to neurotoxicity. Moreover, three-finger toxins may be promising candidates for bioprospecting to develop novel antithrombotic agents. Full article

Background/Objectives: Pit vipers (subfamily Crotalinae) are responsible for a large proportion of snakebite envenoming cases in Southeast Asia. Envenomation by these snakes commonly causes hematotoxic effects, including platelet dysfunction and coagulation disturbances. Although antivenom remains the mainstay of treatment, species-specific antivenoms are not available for several regional pit viper species. This study evaluated the hematotoxic activities of selected Southeast Asian pit viper venoms and the cross-neutralizing capacity of commercially available antivenoms. Methods: Venoms from five medically important pit viper species—Calloselasma rhodostoma, Trimeresurus albolabris, T. hageni, T. purpureomaculatus, and Tropidolaemus wagleri—were tested. Washed platelets and platelet-poor plasma obtained from healthy individuals (n = 10) were used to assess venom-induced platelet aggregation and coagulation, respectively. The neutralizing effects of three antivenoms including hemato polyvalent antivenom (HPAV), T. albolabris antivenom (TAAV), and C. rhodostoma antivenom (CRAV)—were examined in vitro. Results: All tested venoms induced in vitro platelet aggregation (%Max > 50%) and promoted plasma coagulation. At the manufacturer-recommended concentration, TAAV significantly cross-neutralized the hematotoxic effects of T. purpureomaculatus and T. hageni venoms (p < 0.0001) but failed to neutralize coagulation induced by T. wagleri. CRAV showed no cross-neutralization against arboreal pit viper venoms. In contrast, HPAV strongly inhibited platelet aggregation and coagulation induced by all tested venoms (p < 0.0001). Conclusions: These findings highlight the limited cross-neutralization capacity of monovalent antivenoms against arboreal pit viper hematotoxicity. In contrast, HPAV demonstrated broad cross-neutralizing activity and may represent a practical therapeutic option for Southeast Asian pit viper envenoming when species-specific antivenoms are unavailable. Full article

Neurotoxicity caused by snake venom phospholipase A₂ (PLA₂) activity derived from coral snakes (e.g., Micrurus tener, Micrurus fulvius, group IA PLA₂) and some rattlesnakes (e.g., Crotalus scutulatus, group IIA PLA₂) is medically significant. Of interest, the catalytic site of PLA₂ also binds to activated clotting factor X, causing anticoagulation. Given that ruthenium (Ru)-containing compounds have been demonstrated to inactivate hemotoxic venoms in a solvent-dependent manner (e.g., 0.9% NaCl, phosphate-buffered saline), we wished to determine if RuCl₃ would cause solvent-dependent inhibition of snake venom group IA and group IIA PLA₂ in human plasma with thrombelastography. It was determined that RuCl₃ significantly decreased the anticoagulant effects of group IA PLA₂ derived from M. tener and M. fulvius venoms in the presence of 0.9% NaCl, but not phosphate-buffered saline. In contrast, group IIA PLA₂ anticoagulant activity derived from C. scutulatus venom was inhibited by RuCl₃ in both solvents. It is concluded that the different ions formed by RuCl₃ in different solvents may interact with novel disulfide bridges unique to group IA and IIA PLA₂ or through some other mechanism. In vivo validation of Ru-based enzyme inhibitor effects on neurotoxicity associated with either group IA or IIA remains a critical translational issue. Full article

Rhabdophis lateralis is a snake species within the family Natricidae, which is widely distributed across mainland China, Russia, and Korea. Although this species was once thought to be non-venomous, there are quite a few cases demonstrating its bite could be fatal. In this study, we performed de novo assembly and analysis of the transcriptome data from the Duvernoy’s gland of R. lateralis, aiming to characterize its venom transcriptome and reveal the molecular basis of its toxicity. Among 6196 annotated transcripts, 77 were identified as potential toxin transcripts belonging to 26 toxin families. The most highly expressed toxin family was the SVMP family, accounting for 51.10% of the total toxin expression. The other notable toxins included cysteine-rich secretory proteins (CRISPs, 22.36%), c-type lectins (CTLs and snaclecs, 12.13%), and three-finger toxins (3Ftxs, 6.36%). Phylogenetic analyses indicated that SVMPs, CRISPs, and three-finger toxins (3FTxs) are evolutionarily conserved within Colubridae, whereas CTLs likely arose through convergent evolution. All identified SVMPs were classified as P-III type, with one sequence displaying a unique deletion distinct from conventional truncation patterns. The predominantly expressed CTLs are more likely to combine into dimers, exerting coagulation activity. This study provides an insight into the toxin gene expression in the Duvernoy’s gland of R. lateralis, which will benefit future research into the ecological and pharmacological significance of toxins in the genus Rhabdophis. Full article

Snakebite envenoming remains a major global health challenge. Naja atra (N. atra) envenomation induces severe acute kidney injury (AKI), largely driven by snake venom phospholipase A₂ (SVPLA₂). Increasing evidence suggests that immune dysregulation, in addition to direct cytotoxicity, contributes to delayed renal injury. Here, we investigated whether N. atra SVPLA₂ exposure is associated with macrophage immunometabolic remodeling and functional changes relevant to AKI progression. In vivo, AKI was induced in C57BL/6J mice by intraperitoneal administration of N. atra venom, followed by treatment with the SVPLA₂ inhibitor varespladib. In vitro, bone marrow–derived macrophages were exposed to venom with or without varespladib. N. atra venom exposure was associated with extensive tubular apoptosis, increased renal macrophage abundance, and elevated kidney injury biomarkers. Macrophages exhibited a shift toward a pro-inflammatory polarization signature accompanied by reduced efferocytic capacity. Targeted metabolomics revealed coordinated increases in glycolytic intermediates together with upregulation of key glycolytic enzymes. Pharmacological inhibition of SVPLA₂ partially restored macrophage metabolic features and efferocytic capacity and was accompanied by attenuation of renal injury. Together, these findings support a model in which SVPLA₂ exposure is associated with macrophage immunometabolic remodeling and impaired apoptotic cell clearance during venom-induced AKI. Full article

Yamakagashi (Rhabdophis tigrinus) is a widely distributed snake species in Japan. Yamakagashi causes venom-induced consumption coagulopathy (VICC) when the amount of infused venom is high, and bites can be fatal if antivenom treatment is delayed. However, yamakagashi antivenom is an unapproved treatment, and its storage capacity is limited, preventing its prompt administration. Therefore, we investigated the application of commercially available drugs, namely tranexamic acid and antithrombin III, in the treatment of VICC caused by yamakagashi venom in a rat model. Furthermore, we investigated the combination of each drug with recombinant thrombomodulin α. Administration of tranexamic acid or antithrombin III alone failed to extend rat survival or correct changes in blood coagulation markers, such as prothrombin time, fibrinogen concentrations, and D-dimer levels, in yamakagashi venom-treated rats. However, combined administration of recombinant thrombomodulin α and tranexamic acid extended rat survival and partially restored blood coagulation markers. Therefore, the combination of recombinant thrombomodulin α and tranexamic acid might represent a useful therapeutic regimen for yamakagashi venom exposure. Full article

The easily defanged myth that baby rattlesnakes (genera Crotalus and Sistrurus) are more dangerous than adults has persisted in North America despite all evidence to the contrary. The most often cited reason for the babies-more-dangerous (BMD) myth is the venom-dump (VD) hypothesis: babies, in contrast to adults, cannot control how much venom they expend, and therefore inject all of it when biting. We undertook three approaches to explore the origin, transmission, and prevalence of this myth and its most frequent explanation. First, we examined historical newspaper accounts. From 130 newspaper stories mentioning the relative danger of baby rattlesnakes, we identified a timeline in which (1) most stories prior to 1969 were factually correct; (2) the BMD myth and VD hypothesis likely originated in the mid-to-late 1960s and became entrenched in California, especially, from 1970 to 1999; (3) factually incorrect statements subsequently prevailed throughout North America from 2000 to 2014; and (4) factually correct stories regained prominence with apparent effective messaging success from 2015 onward. We further learned that general information stories about rattlesnakes, more often citing subject experts like university professors, were much more likely to provide accurate information than local snakebite stories, which more often cited health professionals (e.g., physicians, veterinarians, pharmacists) and emergency responders (e.g., police and fire officers) who frequently supplied misinformation. Second, we surveyed familiarity with the BMD myth and VD hypothesis among 53 university classrooms (including one high school) representing 3751 students across 29 states within the United States. Consistent with the California media’s outsized influence on misinformation transmission, familiarity with the myth was greatest in the southwestern states (52.6%) and declined moving north and east, with the least familiarity in the northeastern states (16.4%). Third, a small survey of 75 emergency responders and health professionals from Southern California revealed that a whopping 73.3% actually believed the BMD myth. Numerous organizations generally regarded as authoritative further amplified the misinformation, especially on the internet, where some content persists to this day. Unfortunately, belief in the BMD myth and VD hypothesis can lead to negative consequences, including misinformed risk-taking by those encountering snakes, unwarranted fear among snakebite victims, and inappropriate care delivered by misinformed or patient/family-pressured medical professionals. Our findings target health professionals and emergency responders as priority audiences for education. Full article

Background: Lung cancer remains a leading cause of mortality, mainly due to aggressive metastasis and therapeutic resistance. Snake venom metalloproteinases (svMPs), particularly the P-I class, are promising sources for novel antitumor agents. Objectives: This study investigated the impacts of BthMP, a P-I svMPs from Bothrops moojeni venom, on human lung carcinoma (A549) cells in comparison to non-cancerous human bronchial epithelial cells (BEAS-2B). Methods and Results: BthMP demonstrated potent and selective anti-cancer activity. It significantly inhibited key metastatic processes in A549 cells, including adhesion, migration, and invasion, while suppressing long-term proliferation, as shown by reduced colony formation and increased lactate dehydrogenase (LDH) release. Mechanistically, BthMP induced a massive increase in intracellular reactive oxygen species (ROS) by over 2000% and elevated nitric oxide (NO) by 35% in A549 cells, driving a state of lethal oxidative stress. Crucially, these cytotoxic and anti-metastatic effects were minimal in BEAS-2B cells; BthMP even suppressed basal ROS and NO levels in this non-cancerous line. The anti-migratory effects of BthMP were completely dependent on its zinc-based catalytic activity, as they were abolished by pretreatment with ethylenediaminetetraacetic acid. By simultaneously disrupting cell–matrix interactions and inducing selective, catastrophic oxidative stress in cancer cells, BthMP presents a dual-pronged anti-metastatic mechanism. Conclusions: These findings establish BthMP as a promising therapeutic scaffold for developing novel treatments against lung cancer progression. Full article

Background: Snake envenomation represents a significant health concern in some regions of the world, with fatal cases occasionally requiring forensic investigation to estimate the postmortem interval (PMI). However, the influence of venom on carrion decomposition dynamics and arthropod succession patterns remains poorly understood, potentially compromising postmortem interval (PMI) estimations in such cases. Objectives: This study investigated the effects of Naja haje and Cerastes cerastes venoms on decomposition progression and necrophagous arthropod succession. Methods: Fifteen rabbits were allocated into three experimental groups. Two groups received median lethal intravenous doses (LD₅₀) of N. haje or C. cerastes venom, whereas the control group received a saline injection followed by CO₂ euthanasia. The carcasses were subsequently placed under natural field conditions and monitored daily for 15 days. Results: The presence of venom significantly altered decomposition dynamics. C. cerastes venom accelerated early decomposition, shortening both the fresh stage (1 ± 0.22 days vs. 2 ± 0.31 days in controls,) and bloating stage (3 ± 0.35 days vs. 5 ± 0.35 days), while extending both the decay stage (6 ± 0.3 days vs. 6 ± 0.17 days) and the dried stage (5.0 ± 0.44 days vs. 2 ± 0.039 days). N. haje venom showed intermediate effects. Overall arthropod abundance peaked on day 5 and declined thereafter. Control carcasses exhibited significantly higher arthropod abundance than carcasses envenomed with C. cerastes or N. haje. Conclusions: Snake envenomation significantly influenced decomposition kinetics and arthropod colonization patterns. Envenomation with C. cerastes venom produced more pronounced alterations than envenomation with N. haje venom. Full article

Typically, most omics analysis (proteomic and transcriptomic) of snakes are focused on the dominant enzymatic proteins used for evolutionary analysis or those engaged in envenoming symptoms. This study presents a comprehensive multi-assembler transcriptomic analysis focused on the non-dominant and enzymatic or non-enzymatic putative proteins of the venom glands of three medically significant Colombian snake species. Together, these results highlight how continued improvements in modern omics workflows, coupled with extensive manual curation, enable more complete putative protein variants discovery when multiple assemblers are integrated. Here, we reconstructed the toxinomes of the viperids Bothrops asper and Crotalus durissus cumanensis, and the elapid Micrurus mipartitus, by comparing four assemblers (Trinity, SPAdes, SOAPdenovo-Trans k = 31 and k = 97) and integrating them into a non-redundant meta-assembly. Protein-candidate alignments were extensively inspected, and validation of conserved domains and functional motifs are discussed. The curated toxinomes revealed substantial diversity across major and accessory families, and assembler choice strongly affected transcript variant recovery. Together, these results provide a more comprehensive view of venom-gland transcriptome analysis and diversity, expanding the set of candidate venom components for future functional and proteomic validation, with potential implications for venom composition studies and antivenom development. Full article

Phospholipases A₂ (PLA₂s) are key mediators of the cytotoxic and inflammatory activities of snake venoms. While PLA₂ isoforms from Bothrops diporus venom have been characterized and shown to possess antimetastatic and antiangiogenic properties, their impact on mitochondrial bioenergetics and immune modulation has not yet been investigated. In this study, we examined the bioenergetic and immunomodulatory effects of B. diporus PLA₂s using integrated biochemical, metabolic, and multiplex cytokine analyses. In MDA-MB-231 breast cancer cells, pooled PLA₂s induced a dose-dependent decrease in MTT-reducing activity, increased mitochondrial ROS, caused Δψm hyperpolarization, and decreased NADH autofluorescence, collectively indicating sustained mitochondrial stress. Real-time impedance measurements further revealed a marked inhibition of cell proliferation. In human PBMCs, pooled PLA₂s elicited a dynamic cytokine program, inducing early cytotoxic (Granzyme B) and chemotactic (CCL2, CCL3, CCL4) mediators, followed by late pro-inflammatory and regulatory factors such as IL-6, TNF-β, IL-10 and IL-15. Analysis of a single purified PLA₂ isoform (Fraction 6) confirmed activation of the canonical IL-6/TNF-α/IL-1β axis but uniquely induced IL-10 and CCL20, revealing isoform-specific immunomodulatory properties. Altogether, these findings provide the first integrated characterization of mitochondrial and immune perturbations induced by B. diporus PLA₂s, expanding their recognized biological scope and underscoring their potential as molecular templates for novel pharmacological strategies targeting mitochondrial vulnerabilities or modulating the tumor immune microenvironment. Full article

Our current understanding of snake venom is highly biased towards species known to be medically significant in human envenomations. This vastly under-represents the true evolutionary and ecological breadth of snake venom, with gaps spanning entire clades and unique lifestyles. As a result, many genera of rear-fanged snakes lack well-understood venom profiles despite these taxa composing around 65% of known extant snake species. Methodological challenges associated with venom extraction have long been a key reason responsible for the lack of venom research on this group. Modern advancements in venomics technologies have allowed researchers to overcome many of these challenges and investigate the venom components of understudied genera. The genus Coniophanes (black-striped snakes) presents an ideal system for investigating venom and the venom delivery system in a rear-fanged venomous species with well-documented accounts of human envenomations. We sequenced and annotated de novo transcriptomes of the Duvernoy’s gland (DVG) for seven individuals across four species of Coniophanes (Dipsadidae) and confirmed toxin expression in representative venom proteomes. We assessed interspecific venom variation within this genus and further examined intraspecific venom variation within C. imperialis. We found that toxins account for 38.8% to 66% of the total DVG transcriptomes and that 18 toxin families are represented in this genus, with prominent expression of cystine-rich secretory proteins (CRiSPs) in three species and snake venom metalloproteinases (SVMPs) in all four species. In addition, we used diffusible iodine-based contrast-enhanced computed tomography (diceCT) to better understand the venom delivery system for C. fissidens, a widespread species within this genus, showcasing enlarged, grooved, rear fangs in close proximity to a prominent DVG. We provide the first ever characterization of the venom profiles of Coniophanes, highlight venom variation between and within species, and outline the venom delivery system of this understudied genus. Full article

Antivenom administration is currently the only therapy for snakebite envenoming. However, in sub-Saharan Africa, inadequate quality control systems have led to deficits in the availability, accessibility, efficacy and safety of regionally available antivenoms, which, in turn, hinder snakebite treatment and management in the region. To address this impediment to snakebite treatment in Kenya, this study aimed to assess the preclinical neutralising potencies of four different antivenoms previously or currently available in Kenya (SAIMR polyvalent, AFRIVEN, PANAF-Premium^TM and Inoserp^TM) against key snakes of medical importance in the region, towards establishing a national antivenom quality control laboratory. Venoms were extracted from the Kenyan “big five” medically important snake species: Naja ashei, Naja pallida, Naja nigricollis, Dendroaspis polylepis and Bitis arietans, and their lethal potencies were determined using a murine median lethal dose (LD₅₀) assay. In vitro immunological assays (ELISAs and immunoblotting) and an established preclinical murine in vivo neutralisation assay (median effective dose [ED₅₀]) were used to assess the immunoglobulin-binding and venom-neutralising efficacies of the test antivenoms. In vitro assays revealed high venom-binding titres of SAIMR polyvalent, AFRIVEN and PANAF-Premium^TM, and reactivity to a wide range of venom proteins across the different snake venoms. Contrastingly, Inoserp^TM antivenom had low binding titres and poor reactivity to the snake venom proteins. These findings were aligned with the in vivo results, where SAIMR polyvalent, AFRIVEN and PANAF-Premium^TM showed potent venom-neutralising efficacies against all the tested snake venoms, while Inoserp^TM had low potency and failed to neutralise the lethal effects of N. ashei, N. pallida and D. polylepis venoms at the manufacture-claimed doses. Based on these robust preclinical results, we conclude that SAIMR polyvalent, AFRIVEN and PANAF-Premium^TM antivenoms offer considerable potential for the treatment of envenoming by diverse medically important snakes in Kenya. The observed deficiencies with the Inoserp^TM product highlight the importance of (i) robust, independent preclinical antivenom efficacy testing and (ii) the value of establishing a quality control laboratory to inform local regulatory and procurement decision making. Full article