Search Results (94)

Coral snakes of the American continent are classified into two genera, Micruroides and Micrurus, with as many as 91 species recognized in the latter. Although envenomings caused by Micrurus are rare, they can be life-threatening due to neurotoxic effects leading to flaccid paralysis and potential respiratory failure. Micrurus ancoralis is found in the Pacific lowlands and along the western slope of the cordillera occidental Cordillera in Colombia. Although this species is relatively common within its distribution range, its phylogenetic position and the characterization of its venom have not been investigated. The results of phylogenetic analysis placed M. ancoralis within the triadal/bicolor clade of species with the characteristic triad pattern and group bicolor. Proteomic characterization of the venom showed predominance of phospholipase A₂ (PLA₂) enzymes in its composition, with 51.7% of the total protein content, followed by three-finger toxins (3FTxs; 23.2%) and lower proportions of proteins belonging to several other minor families. Out of 28 chromatographic venom fractions obtained, the seven most abundant were evaluated for toxicity, with three of them (F7, identified as a 3FTx, and F18 and F20 (both identified as PLA₂s)) showing lethal activity by the intraperitoneal route in mice. The PLA₂ activity of F20 was confirmed and its edema-inducing, myotoxic, and lethal effects in mice were demonstrated. A therapeutic equine anti-coral antivenom (INS, Colombia) against coral snake envenomings immunorecognized the whole venom and its fractions in ELISA tests and was able to neutralize 2 × LD₅₀ (medial lethal dose) of M. ancoralis venom by preincubation, with an estimated potency of at least 0.2 mg venom/mL antivenom. This result suggests that envenomings by M. ancoralis could be effectively treated by this antivenom. Full article

Snakebite envenoming is a neglected tropical disease causing approximately 81,410–137,880 deaths globally each year and four-fold more disabilities than mortality rate. Despite the availability of antivenoms for treatment, several in vitro and in vivo preclinical studies have shown that their efficacy is limited by many factors including regional venom variation and poor neutralization of major venom toxins. To address these limitations, the potential of alternatives including aptamers, recombinant monoclonal antibodies, camelid antibodies, small molecule inhibitors, and natural product-based inhibitors targeting key venom proteins have been explored. Among these, small molecule inhibitors targeting key enzymatic snake venom proteins are emerging as adjuvants to antivenom treatment. Most of these small molecules are repurposed drugs with established safety, oral bioavailability, and lower cost compared to antivenoms. In this regard, this review tries to compile available information regarding the use of small molecule inhibitors to counteract envenomation with special emphasis on three major enzymatic snake venom protein families: phospholipase A₂, snake venom metalloproteinases, and snake venom serine proteases. In vitro studies have shown that these small molecule inhibitors used either alone or in combination with antivenom can potentially reduce the adverse effects of venom-induced coagulopathy, neurotoxicity, tissue damage, and inflammation. However, critical gaps remain including limited human clinical trial data, uncertain efficacy across diverse venoms, and undefined dosing strategies. Overall, small molecules represent a mechanistically targeted and clinically promising adjunct to antivenom therapy, warranting further validation through randomized trials, pharmacokinetic studies, and development of field-applicable treatment protocols. Full article

Azemiops feae (Fea’s viper) is a phylogenetically distinctive Asian viper with poorly defined medical significance, and human envenomations remain rarely reported in the English-language literature. We describe a new case of A. feae envenoming from Chongqing, China, and present a scoping review of published clinical case reports and case series to better characterize its epidemiology, clinical manifestations, and management. A 53-year-old male developed marked local pain and swelling following a bite to the hand, accompanied by transient neurotoxic symptoms, as well as mild hypofibrinogenemia. Treatment with a single vial of Gloydius brevicaudus monovalent antivenom was followed by clinical improvement and full recovery. Review of the literature identified nine previously published studies from China and one captive case from Europe. Envenoming typically occurred during agricultural activities, most commonly affected the lower extremities, and was characterized by prominent local effects with occasional mild neurotoxic features and inconsistent, generally mild coagulation abnormalities. Antivenom use was highly variable, involving multiple heterologous monovalent antivenoms, and outcomes were uniformly favourable regardless of antivenom administration. Collectively, available evidence indicates that A. feae envenoming is usually self-limited, with predominantly local effects and infrequent, mild systemic involvement. However, the absence of species-specific antivenom and the heterogeneity of current treatment practices highlight the need for systematic venom characterization and functional antivenom efficacy studies to inform evidence-based clinical management. Full article

In Croatia, the European Viper Venom Antiserum^®, produced by the Institute of Immunology Zagreb, was the only antiserum used to treat Vipera ammodytes envenomation. When production of the Zagreb antivenom ceased, three other antivenoms, Viperfav^®, BulBio^®, and Viekvin^®, replaced it in clinical practice at the Department of Infectious Diseases, University Hospital Split. This study includes 34 patients envenomed by Vipera ammodytes during the period between 2020 and 2025: 24 (71%) suffered grade 2a envenomation, nine (26%) grade 2b, and one grade 3 (severe envenomation). None were admitted to the Intensive Care Unit. All patients received antivenom: 16 received Viperfav^®, 17 BulBio^®, and one Viekvin^®. All grade 2a patients were treated with a single dose of antivenom. Among grade 2b patients, four received one dose and two received two doses of Viperfav^®, while one received one dose and two received two doses of BulBio^®. The grade 3 patient received two doses of BulBio^®. In all cases, treatment was successful and patients were discharged from hospital after an average of 3.97 days. Patients with pronounced neurotoxic signs did not require treatment with multiple doses of antivenom. All antivenoms proved effective. No adverse reactions or fatalities were observed. Full article

Asian coral snakes are distributed throughout Southeast Asia, including Thailand, but clinical data on their envenomation remain limited. Using a 10-year retrospective dataset from the Ramathibodi Poison Center, we investigated the epidemiology, clinical characteristics, management, and outcomes of Asian coral snake envenomation in Thailand. Patient demographics, clinical and laboratory data, treatments, and outcomes were analyzed descriptively. Fifty-two patients were included. Sinomicrurus macclellandi was the most frequently reported species. Most bites occurred during the rainy season and involved the lower extremities. Clinical manifestations were predominantly mild and localized. No cases of systemic neurotoxicity, bulbar weakness, respiratory compromise, or death were observed. Laboratory results were generally within normal limits. Two patients developed anaphylaxis, which resolved with standard emergency treatment, while two experienced severe pain. Calliophis intestinalis lineata was associated with a higher proportion of tachycardia at presentation and longer hospitalization. No patients required mechanical ventilation or antivenom therapy. Supportive care and short-term hospital observation are generally sufficient in confirmed cases. The median duration of hospitalization was 1–3 day. Local manifestations were the predominant clinical findings following Asian coral snake envenomation in Thailand, and systemic neurotoxicity was not observed. These findings differ from reports of Micrurus envenomation, which primarily involve New World coral snakes, whereas the species implicated in Thailand belong to Old World genera. Full article

Snakebite envenomation (SBE) is a major public health issue in sub-Saharan Africa (SSA), particularly in Cameroon. This Phase IV, multicenter, open-label study was conducted from June 2024 to December 2024 to evaluate the safety and efficacy of PANAF-Premium™, a World Health Organization (WHO)-approved polyvalent antivenom that was introduced in Cameroon in 2023, given that prospectively gathered data and studies on this antivenom’s safety in SSA are limited. In total, 130 victims admitted to four district hospitals in North Cameroon with confirmed SBE were included. Data on envenomation syndromes, clinical outcomes, adverse events, and treatment response were recorded. Echis species were responsible for most bites, while clinical syndromes included hemotoxic (68.5%), cytotoxic (30.8%), and neurotoxic (0.8%) presentations. On average, victims required 3.34 vials and 5.55 days for clinical recovery. Early antivenom administration significantly reduced the number of antivenom vials required to manage the symptoms (p = 0.003) and hospital stay (p = 0.049). Seventeen patients experienced mild to moderate adverse events. Two deaths and a case of kidney injury were noted, all unrelated to antivenom use. These study findings indicate the safety and effectiveness of PANAF-Premium™ antivenom, meeting WHO performance targets. The results highlight the importance of timely antivenom administration in treating SBEs. Full article

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

Neurotoxicity following South American Crotalus rattlesnake bite is primarily caused by crotoxin, the most abundant component in their venom. Despite the central role of voltage-gated calcium channels (Ca_V) in neurotransmission, direct targetability by crotoxin has been poorly explored. Crotoxin is a non-covalent heterodimer formed by an acidic subunit (CA) and a basic toxic phospholipase A₂ subunit (CB). Here, we chromatographically isolated the CB subunit from Crotalus vegrandis and studied its effect on Ca_V heterologously expressed in tsA201 cells using the whole-cell patch-clamp technique. Mass spectrometry analysis identified a protein that matched with 97% sequence coverage the CBc isoform from Crotalus durissus terrificus. Isolated CB exhibited moderate phospholipase activity that was not correlated to its cytotoxic effect on cultured tsA201 cells. Using Ba²⁺ as a charge carrier to prevent the enzymatic activity, we found that CB inhibited currents mediated by the N-type Ca_V2.2 and Ca_V1.2 L-type calcium channels, in a dose–dependent manner, with higher potency for the latter, and negligible changes in the voltage dependence of channel activation. Our results reveal a novel phospholipase-independent biological activity and a molecular target of CB providing new insights into the pathophysiology of Crotalus snakebite envenoming with potential clinical therapeutic implications. Full article

Background: Cobras (Naja sp.) are medically important snakes in Thailand. Envenoming by the monocled cobra (N. kaouthia) often causes neurotoxicity, most notably ptosis, ophthalmoplegia, local tissue necrosis and progressive paralysis leading to respiratory failure. Early antivenom administration and respiratory support are medically significant for effective treatment. Methods: In this study, we determined the association between the time course of cobra envenoming and related neurotoxic outcomes using the clinical profiles of cobra envenomed patients. We also demonstrated histopathological changes in the neuromuscular junction of the diaphragm in experimentally envenomed rats. Results: A retrospective study of 69 cases of cobra envenoming in Central and Southern Thailand shows that delayed arrival beyond one hour at hospital was common among younger adults (47.0% aged 10–29) and associated with more severe neurotoxicity, including higher rates of ptosis (41.2%, p = 0.032) and referrals (41.2% vs. 15.4%, p = 0.040). Antivenoms (22 Monovalent and 1 Polyvalent) were administered to 23 (33.3%) envenomed victims and caused adverse reactions in 9 cases (39.1%). Neurotoxicity following cobra envenoming in the clinical section correlated with histopathological examination of envenomed rat diaphragms. Transmission electron microscopy (TEM) revealed degeneration of the neuromuscular junction and diaphragm within 1 h following experimental cobra envenomation, which worsened by 4 h. Intravenous administration of antivenom at recommended doses reduced diaphragmatic damage but failed to prevent presynaptic degeneration after 90 min of envenoming. Conclusions: Clinically, extraocular muscle paralysis was the earliest manifestation. Early monitoring and prompt administration of antivenom are essential to reduce neurotoxicity and relevant complications. Full article

In China, bites caused by the Naja atra and Deinagkistrodona acutus are the most common types of snakebites. While the functional characteristics of the two venom components have been well documented, their in vivo metabolic pathways, target organ distribution patterns, and dynamic pharmacokinetic profiles remain less explored. This study established a murine envenoming model through CY7-SE labeling of Naja atra and Deinagkistrodon acutus venoms. The real-time in vivo absorption and biodistribution of venoms were dynamically monitored via fluorescence imaging, with subsequent proteomic profiling to characterize organ-specific toxin targeting patterns. Gel filtration chromatography and HPLC analyses validated labeling efficiency at ratios of 0.1 mg CY7-SE per 1 mg Naja atra venom and 0.075 mg CY7-SE per 1 mg Deinagkistrodon acutus venom, with electrophoretic confirmation of protein integrity and preserved 740 nm fluorescence excitation. Acute toxicity assays demonstrated no significant difference in LD₅₀ lethality between labeled and native venoms (p > 0.05). The intoxication models revealed species-specific pathophenotypes, i.e., CY7-Naja atra venom induced systemic weakness, tachypnea, and inflammatory necrosis in lung, myocardium, and liver, whereas CY7-Deinagkistrodon acutus venom provoked hemorrhagic diathesis. Both models exhibited marked leukocytosis, transaminitis, and elevated creatinine levels (p < 0.05). Fluorescence tracing uncovered distinct biodistribution kinetics: Deinagkistrodon acutus venom achieved peak organ accumulation at 3 h with rapid dissemination (24 h injection-site retention: 12.61%), contrasting with Naja atra venom’s delayed 6 h peak and prolonged renal sequestration (24 h injection-site retention: 60.9%). Target organ proteomic profiling identified Deinagkistrodon acutus-enriched thrombin-like enzymes and metalloproteinases in lung/liver/spleen, while Naja atra venom predominantly accumulated renal acidic phospholipase A₂ and weakly neurotoxic NNAM2. Full article

Lancehead pitvipers, Bothrops snakes, or, popularly, “jararacas”, are common and broadly distributed in the Americas, especially in Brazil, where they are responsible for causing a high number of snakebite accidents. Their venoms are able to induce local and systemic effects, such as hemorrhaging, acute kidney failure, and shock, that can be fatal. Among the compounds of the venom are phospholipases A₂ (PLA₂s), which are abundant in some Bothrops species. PLA₂s can perform different activities during envenoming, such as neurotoxicity, myotoxicity, and cytotoxicity, among others, through the hydrolysis of the ester bond at the sn-2 position of phospholipids, producing free fatty acids and lysophospholipids. Although different PLA₂s can be classified into different PLA₂ groups and subgroups, according to structure, function, size, localization and Ca²⁺ dependence, they converge to be available in biotechnological and therapeutic applications, such as antiviral and antitumor, among others, being relevant molecules to be deeply studied. Here, we provide the state of the art of PLA₂s, found in snake venoms, focusing on Bothrops venoms, as well as their potential applications, beyond their inhibitors, that also receive attention due their importance in PLA₂ studies and diverse applications. Full article

The genus Oxyuranus, which includes some of the most venomous snakes in the world, presents a complex venom composition with potent neurotoxic and procoagulant effects. This study provides a comparative proteomic analysis of the venom of Oxyuranus microlepidotus (Inland Taipan) and Oxyuranus scutellatus (Coastal Taipan), aiming to elucidate the molecular basis underlying their distinct toxicological profiles. Using high-resolution chromatographic fractionation and LC-MS/MS, we identified a core set of nine protein families shared between both species, including phospholipases A₂ (PLA₂), three-finger toxins (3FTx), natriuretic peptides (NTP), nerve growth factors (NGF), and prothrombin activators (PTA). O. microlepidotus venom exhibited greater diversity of 3FTxs and unique protein families, such as Waprin and 5′-nucleotidases, suggesting lineage-specific functional adaptations. Quantitative analysis revealed a greater relative abundance of PLA₂s in O. scutellatus (66%) compared to O. microlepidotus (47%), whereas 3FTXs were more prominent in O. microlepidotus (33% vs. 9%). These interspecific differences likely underlie the distinct clinical manifestations of envenomation and reflect evolutionary divergence in the venom composition. Our findings provide molecular insights into taipan venom complexity and highlight novel toxin candidates with potential biomedical applications in neurobiology, hemostasis, and anti-infective therapy. Full article

Mamba (Dendroaspis species) snakebites are critical medical emergencies across sub-Saharan Africa. Envenomings can result in the rapid onset of complex neurotoxic symptoms, often leading to high rates of mortality without timely intervention with antivenom. The ancestral state of mambas is the green coloured, forest dwelling type, with the tan/grey coloured, savannah dwelling D. polylepis (Black Mamba) representing a derived state both ecologically and morphologically. However, it has not been tested whether these changes are paralleled by changes in venom biochemistry or if there are differential molecular evolutionary patterns. To fill these knowledge gaps, this study evaluated the neurotoxic effects of all Dendroaspis species venoms using the chick biventer cervicis nerve-muscle preparation, assessed the neutralizing efficacy of three antivenoms commercially available in Africa, and reconstructed the molecular evolutionary history of the toxin types to ascertain whether some were unique to particular species. All Dendroaspis venoms demonstrated potent flaccid-paralysis due to postsynaptic neurotoxicity. The only exception was D. angusticeps venom, which conversely exhibited spastic-paralysis due to presynaptic/synaptic neurotoxicity characterised by potentiation of acetylcholine presynaptic release and sustained synaptic activity of this neurotransmitter. Antivenom efficacy varied significantly. All three antivenoms neutralized to some degree the flaccid-paralysis postsynaptic effects for all species, with D. viridis venom being the best neutralized, and this pattern extended to all the antivenoms. However, neutralisation of flaccid-paralysis postsynaptic effects unmasked spastic-paralysis presynaptic/synaptic neurotoxicity within non-angusticeps venoms. Spastic-paralysis presynaptic effects were poorly neutralized for all species by all antivenoms, consistent with prior clinical reports of poor neutralisation of spastic-paralytic effects. Geographic variation in D. polylepis venom was evident for the relative neutralisation of both spastic-paralysis presynaptic/synaptic and flaccid-paralysis postsynaptic/synaptic neurotoxic pathophysiological effects, with differential neutralization capabilities noted between the Kenyan and South African populations studied. Molecular phylogenetic analyses confirmed spastic-paralysis and flaccid- paralysis toxins to be a trait that emerged in the Dendroaspis last common ancestor, with all species sharing all toxin types. Therefore, differences in venoms’ pathophysiological actions between species are due to differential expression of toxin isoforms rather than the evolution of species-specific novel toxins. Our findings highlight the synergistic nature of flaccid-paralysis postsynaptic and spastic-paralysis presynaptic/synaptic toxins, while contributing significant clinical and evolutionary knowledge of Dendroaspis venoms. These data are crucial for the continued development of more effective therapeutic interventions to improve clinical outcomes and for evidence-based design of clinical management strategies for the envenomed patient. Full article

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

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