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Search Results (289)

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Keywords = snake envenomation

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19 pages, 3670 KB  
Article
Early Clinical Approach Prevents Severe Neurotoxicity Following Cobra Envenoming: An Integrated Experimental and Multi-Center Clinical Study in Thailand
by Sethapong Lertsakulbunlue, Musleeha Chesor, Panuwat Promsorn, Wanida Chuaikhongthong, Wipapan Khimmaktong, Wittawat Chantkran and Janeyuth Chaisakul
Biomedicines 2026, 14(1), 144; https://doi.org/10.3390/biomedicines14010144 (registering DOI) - 10 Jan 2026
Abstract
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 [...] Read more.
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
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13 pages, 1482 KB  
Article
Characterization of Alpha-Bungarotoxin Antibodies Prepared by Different Strategies
by Huijuan Lu, Guowen Zhang, Lin Zhao, Ying Yuan, Bing Gong, Bin Han and Wen-Hui Lee
Toxins 2025, 17(12), 601; https://doi.org/10.3390/toxins17120601 - 16 Dec 2025
Viewed by 347
Abstract
The preparation of an antibody to treat snake envenomation requires a large amount of snake venom. In China, only four types of anti-snake venom sera are clinically available, and the production and immunization strategies for clinically approved anti-snake venom sera still mainly rely [...] Read more.
The preparation of an antibody to treat snake envenomation requires a large amount of snake venom. In China, only four types of anti-snake venom sera are clinically available, and the production and immunization strategies for clinically approved anti-snake venom sera still mainly rely on detoxified antigens, which is a mature technical route commonly adopted by domestic pharmaceutical enterprises. At present, researchers immunize animals with low doses of certain snake venom toxic components or prokaryotically expressed toxic components to reduce the amount of venom needed, and use prepared antisera for their specific investigation purposes. However, it is unclear if low-dose immunized antibody titers and toxin-neutralizing activities are consistent with those of high-dose detoxified crude venom immunized antibodies. In this study, we developed a method for the preparation of highly effective rabbit polyclonal antisera while saving a large amount of toxin. Rabbit polyclonal antisera prepared by low-dose natural α-bungarotoxin (α-BGT) had strong neutralizing effects on the toxin itself and achieved the same antibody titers as antisera prepared with high doses of detoxified α-BGT. Antigen of A maltose binding protein (MBP) fused with α-BGT (MBP-α-BGT) expressed in prokaryotes had low antibody titer and low neutralizing activity. This study provides an effective dosage selection guide and methods for the preparation of polyclonal antibodies and antiserum for investigation purposes. Full article
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11 pages, 343 KB  
Article
Quality and Reliability of YouTube Videos on Poisonings, Insect Bites, and Envenomations
by Ali Halici, Behçet Demir and Çağla Özdemir
Healthcare 2025, 13(24), 3224; https://doi.org/10.3390/healthcare13243224 - 10 Dec 2025
Viewed by 320
Abstract
Background: YouTube has become one of the most widely used platforms for medical education and patient information. However, the accuracy and reliability of such unregulated content remain highly variable and sometimes misleading. This study aimed to evaluate the quality, reliability, and educational [...] Read more.
Background: YouTube has become one of the most widely used platforms for medical education and patient information. However, the accuracy and reliability of such unregulated content remain highly variable and sometimes misleading. This study aimed to evaluate the quality, reliability, and educational value of YouTube videos related to poisonings, insect bites, and envenomations using validated scoring systems. Methods: A cross-sectional analysis of YouTube videos was conducted using the search terms “approach to insect bites and stings,” “approach to poisonings,” “approach to scorpion envenomation,” “approach to snake envenomation,” and “approach to mushroom poisoning.” Searches were performed in incognito mode on August 1, 2025. Only English-language videos shorter than one hour were included. Video quality and reliability were evaluated using the Global Quality Score (GQS), modified DISCERN (mDISCERN), and Journal of the American Medical Association (JAMA) benchmarks, while viewer engagement was measured using the Video Power Index (VPI). Results: A total of 279 videos were analyzed. The mean ± SD scores were as follows: GQS, 3.53 ± 1.09; mDISCERN, 3.53 ± 1.08; and JAMA, 2.63 ± 0.96. Based on the GQS, 59.5% of the videos were high quality, 20.8% moderate quality, and 19.7% low quality; thus, approximately 40% of the evaluated videos (low- and moderate-quality categories combined) did not meet optimal quality standards. Videos on snake envenomation and general poisoning had significantly higher quality and reliability scores (p < 0.001). Educational, physician-sourced, and physician-presented videos achieved higher GQS, JAMA, and mDISCERN values (p < 0.001 for all). However, no significant differences were found in the VPI, indicating that popularity metrics did not correlate with content quality. Conclusions: YouTube provides wide access to poisoning-related educational materials, but content quality varies considerably, and a substantial proportion of videos fall below acceptable quality thresholds. Videos produced or presented by physicians are more reliable, whereas popularity is not a valid indicator of scientific accuracy. Active involvement of healthcare professionals and academic institutions, together with platform-level quality verification and visibility strategies, is essential to improve the credibility and impact of online health information. Full article
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12 pages, 241 KB  
Article
Epidemiological and Clinical Behavior of Snakebite in the Pediatric Population, Associated with a Logistic Regression Model
by Cándida Revollo Vargas, Osnamir Bru-Cordero and Karina Pastor-Sierra
Clin. Pract. 2025, 15(12), 228; https://doi.org/10.3390/clinpract15120228 - 5 Dec 2025
Cited by 1 | Viewed by 259
Abstract
Introduction: Snakebite envenomation is recognized by the World Health Organization (WHO) as a neglected tropical disease. In Colombia, snakebites are frequent due to the diversity of ecosystems and snake species, and children represent a particularly vulnerable population. Objective: This study aimed to characterize [...] Read more.
Introduction: Snakebite envenomation is recognized by the World Health Organization (WHO) as a neglected tropical disease. In Colombia, snakebites are frequent due to the diversity of ecosystems and snake species, and children represent a particularly vulnerable population. Objective: This study aimed to characterize the epidemiological and clinical behavior of snakebite envenomation in the pediatric population and to identify factors associated with its severity through the application of a multinomial logistic regression model. Methods: An exploratory analysis was conducted on 170 pediatric patients reported to the Public Health Surveillance System (SIVIGILA) and treated at San Jerónimo Hospital in Montería (HSJ). Sociodemographic and clinical data were collected, and a multinomial logistic regression model was applied to identify risk factors associated with the severity of envenomation. Results: Most cases occurred in children over 12 years of age (51.8%), and males were the most affected. The lower limbs were the most common site of the bite (87.6%). Bothrops was the main genus responsible. Non-medical practices, such as herbal poultices and potions, were reported in 28.2% of cases. Clinically, moderate envenomation was the most frequent (48.2%), with edema (88%) and pain (92%) as the main local manifestations, and nausea (36%) and vomiting (32%) as systemic manifestations. Cellulitis was the most common complication (24%). Student’s t-test showed a significant difference between complications and hospital stays lasting 3 to 7 days. The multinomial logistic regression explained 75% of the severity variability and showed that prior non-medical practices increased the risk of severe cases. Conclusions: Snakebite envenomation in children remains an important public health problem. The statistical model showed that non-medical practices are associated with a higher degree of severity. Full article
18 pages, 5407 KB  
Article
Differential Effects of Marimastat and Prinomastat on the Metalloprotease Activity of Various Snake Venoms
by Mahtab Khatibi, José R. Almeida, Soheil Gilabadi, David Ramírez, Paulina Valenzuela-Hormazábal, Ketan Patel and Sakthivel Vaiyapuri
Toxins 2025, 17(12), 571; https://doi.org/10.3390/toxins17120571 - 26 Nov 2025
Viewed by 970
Abstract
Snakebite envenoming is a neglected tropical disease, responsible for approximately 140,000 deaths globally each year. Vipers and elapid snakes represent the most significant snake families in medical contexts, exhibiting a variety of venom components and clinical effects in bite victims. Metalloproteases, a primary [...] Read more.
Snakebite envenoming is a neglected tropical disease, responsible for approximately 140,000 deaths globally each year. Vipers and elapid snakes represent the most significant snake families in medical contexts, exhibiting a variety of venom components and clinical effects in bite victims. Metalloproteases, a primary component of venoms, are mainly accountable for haemotoxic and myotoxic effects. Although predominantly found in viper venoms, these enzymes are also present in varying levels in elapid snake venoms. Marimastat and prinomastat are matrix metalloprotease inhibitors initially developed as cancer therapies. Recently, extensive research has focused on these inhibitors to neutralise venom metalloproteases. However, their effects on different viper and elapid snake venoms remain unclear. Here, we report the sensitivity of seven elapid venoms (specifically, cobras) and 12 viper venoms to marimastat and prinomastat, utilising selective in vitro experiments and molecular docking analyses performed using representative metalloprotease (VAP2, a viper metalloprotease from the venom of Crotalus atrox and an elapid metalloprotease from the venom of Naja atra) structures. Both compounds inhibited the metalloprotease, fibrinogenolytic, and caseinolytic activities of most viper venoms. While prinomastat displayed prominent inhibitory effects on cobra venoms in these assays, marimastat demonstrated limited inhibitory effects on these venoms. These findings illustrate the role of matrix metalloprotease inhibitors in modulating metalloprotease activities across a range of viper and cobra venoms. Collectively, this study establishes the differential effects of marimastat and prinomastat on various levels of metalloproteases present in viper and elapid venoms. This will enhance understanding of the abundance of metalloproteases in snake venoms and their sensitivity to different matrix metalloprotease inhibitors. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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14 pages, 2282 KB  
Case Report
Molecular Mechanisms of Efficacy Variation in Antivenoms: Insights from a Malayan Pit Viper (Calloselasma rhodostoma) Bite in Vietnam
by Thuan Quang Le, Nguyen Trung Nguyen, Yen Bao Pham, Minh Bao Vu, Nhan Thanh Le, Nhan Sy Pham Nguyen, Neil R. Balchan, Choo Hock Tan, Thai Huu Duong, Hoang Huy Nguyen and Tao Thien Nguyen
Trop. Med. Infect. Dis. 2025, 10(12), 331; https://doi.org/10.3390/tropicalmed10120331 - 25 Nov 2025
Viewed by 511
Abstract
Background: Although antivenom is the standard treatment for snakebite envenoming, its efficacy may be impacted by geographic variation in venom composition, emphasizing the need for region-specific antivenom development. Methods: We report a case of snakebite envenoming, in which the patient was bitten on [...] Read more.
Background: Although antivenom is the standard treatment for snakebite envenoming, its efficacy may be impacted by geographic variation in venom composition, emphasizing the need for region-specific antivenom development. Methods: We report a case of snakebite envenoming, in which the patient was bitten on the hand by a captive Malayan pit viper (Calloselasma rhodostoma) with typical clinical manifestations following. Antivenom (produced in Thailand) was administered at 33 and 39 h post-bite. Venom from the causative individual snake was collected for compositional analysis via SDS-PAGE. Enzymatic activity of the venom was evaluated through the degradation of casein and phospholipid substrates, along with the assessment of enzymatic inhibition by two regionally specific antivenoms produced in Vietnam (AV. Cr. VN.) and Thailand (AV. Cr. TL.). Results: The patient showed good recovery, with complete normalization by day 7. SDS-PAGE profiling of the venom revealed five major enzymes, with SVSP, SVMP and PLA2 being the most abundant (16.7%, 40.11% and 26.11%, respectively). Antivenom inhibition tests revealed remaining casein percentages of 67.43% (AV. Cr. VN) and 59.35% (AV. Cr. TL). Blood agar assays indicated that phospholipase activity was reduced to 21.01% by AV. Cr. VN. and 23.30% by AV. Cr. TL. Conclusions: Our results show that the Vietnamese antivenom generated greater inhibitory activity against proteinases compared to the Thai product, underscoring the importance of using regionally specific antivenoms that are more effective against the venom profiles of locality-matched snake populations. Full article
(This article belongs to the Special Issue Recent Advances in Snakebite Envenoming Research)
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29 pages, 3838 KB  
Review
Phospholipases A2 (PLA2s) and Related Peptides from Bothrops Snake Venoms: History, Structure, Pharmacology, and Inhibitors
by Isabela C. dos Santos, Marcela Romanazzi, Geovanna M. Malachias-Pires, Ariani R. Aragão, Eloise T. M. Filardi, Guilherme Melo-dos-Santos, Lara C. Salvador, Marcos F. Cerveja, Anderson M. Rocha, Ananda Magalhães, Isadora S. de Oliveira, José R. Almeida, Norival A. Santos-Filho and Manuela B. Pucca
Biomolecules 2025, 15(11), 1583; https://doi.org/10.3390/biom15111583 - 11 Nov 2025
Viewed by 1015
Abstract
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, [...] Read more.
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
(This article belongs to the Section Natural and Bio-derived Molecules)
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14 pages, 8136 KB  
Article
Snake Venom C-Type Lectin-like Protein Vaa-Snaclec-3/2 Efficiently Prevents Carotid Artery Thrombosis in a Mouse Model Without Compromising Blood Coagulation
by Monika C. Žužek, Igor Križaj, Miran Brvar, Tomaž Trobec, Simona Kranjc Brezar, Mojca Dobaja Borak, Adrijana Leonardi, Kity Požek, Milka Vrecl and Robert Frangež
Toxins 2025, 17(11), 523; https://doi.org/10.3390/toxins17110523 - 23 Oct 2025
Cited by 1 | Viewed by 1013
Abstract
Platelets play pivotal roles in thromboembolic diseases, such as myocardial infarction and ischemic stroke. In patients envenomed by the snake Vipera a. ammodytes (Vaa), pronounced and transient thrombocytopenia without bleeding is observed. We previously showed that Vaa-snaclec-3/2, the snake venom [...] Read more.
Platelets play pivotal roles in thromboembolic diseases, such as myocardial infarction and ischemic stroke. In patients envenomed by the snake Vipera a. ammodytes (Vaa), pronounced and transient thrombocytopenia without bleeding is observed. We previously showed that Vaa-snaclec-3/2, the snake venom C-type lectin-like protein, mediates this effect ex vivo. Here, we extended our study of the antithrombotic potential of this protein in vivo using a mouse model of ferric chloride (FeCl3)-induced carotid artery thrombosis. Prior to inducing thrombus formation, the mice received 1, 5, 10, 20, or 50 μg/kg Vaa-snaclec-3/2 intravenously. Afterward, the arterial blood flow was monitored with a perivascular Doppler probe. Additionally, the platelet count in the peripheral venous blood; tail bleeding time; and liver, lung, kidney, spleen, and heart histology were evaluated. The lowest dose of Vaa-snaclec-3/2 that we showed to cause severe thrombocytopenia and completely inhibit FeCl3-induced thrombus formation was 20 µg/kg. This dose prolonged the median tail bleeding time from 86.5 to 153.5 s but did not induce acute spontaneous hemorrhage, as demonstrated by histological analysis. Histology revealed no signs of apoptosis, necrosis or other degenerative changes in the inspected organs of mice exposed to 20 μg/kg Vaa-snaclec-3/2. Platelet clusters were observed only in the lungs, which appear to be the primary site of platelet sequestration and the cause of thrombocytopenia. Taken together, our findings highlight the high potential of Vaa-snaclec-3/2 as a safe and effective antithrombotic agent for the transient prevention of thrombosis in acute clinical settings. Full article
(This article belongs to the Special Issue Animals Venom in Drug Discovery: A Valuable Therapeutic Tool)
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21 pages, 3094 KB  
Article
Comparative Proteomics, Functional Characterization and Immunological Cross-Reactivity Studies on Russell’s Viper Venom from Two Distinct Geographical Regions in South India
by Nisha Reghu, Sudharshan Rao, Dileepkumar Raveendran, Bipin Gopalakrishnan Nair and Muralidharan Vanuopadath
Int. J. Mol. Sci. 2025, 26(19), 9734; https://doi.org/10.3390/ijms26199734 - 7 Oct 2025
Viewed by 1090
Abstract
Snakebite envenoming is a neglected tropical disease contributing to a significant number of morbidities and mortalities globally. Reports indicate that venom variation influences antivenom efficacy, which might affect treatment outcomes. The venom composition of Daboia russelii (Russell’s viper), one of the big four [...] Read more.
Snakebite envenoming is a neglected tropical disease contributing to a significant number of morbidities and mortalities globally. Reports indicate that venom variation influences antivenom efficacy, which might affect treatment outcomes. The venom composition of Daboia russelii (Russell’s viper), one of the big four snakes in India, has been extensively studied from different geographical regions of India. Nonetheless, the Russell’s viper venom proteome from Kerala (Western Ghats region), together with its study in comparison with the same species’ venom from Tamil Nadu, has not been explored yet. In the current study, Daboia russelii venom from Irula (RVi) and the Western Ghats region in Kerala (RVwg) was characterized through mass spectrometry-based proteomics and few functional assays. The proteomics study identified 52 proteins from 14 snake protein families in RVi and 61 proteins from 17 snake venom protein families in RVwg. Some of the protein families, including DNase and hyaluronidase, as well as vascular endothelial growth factor, were exclusively identified in RVwg venom. Comparative functional analysis indicated that RVwg exhibited higher fibrinogenolytic and hyaluronidase activities, while RVi venom showed higher phospholipase A2 and L-amino acid oxidase activities. Through ELISA, RVi venom showed an end-point titration value of 1:24,300 for all the antivenoms used in this study, whereas for RVwg, compared to PSAV (Premium serums and vaccines) (1:2700), Virchow and VINS (both 1:8100) antivenoms showed better immunological cross-reactivity. Immunoblotting experiments indicated differential binding and recognition of antigenic epitopes present in both venoms by the polyvalent antivenoms used in the current study. All these findings highlight that the venom proteome varies according to the geographical location, and this significantly influences antivenom efficacy. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Venom and Antivenom)
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20 pages, 6584 KB  
Article
Compromised Regeneration, Damage to Blood Vessels and the Endomysium Underpin Permanent Muscle Damage Induced by Puff Adder (Bitis arietans) Venom
by Sodiq Opeyemi Adeyemi, Nicholas John Richards, Ali Alqallaf, Husain Bin Haidar, Mustafa Jawad Jalil Al-Asady, Jarred Williams, José R. Almeida and Ketan Patel
Toxins 2025, 17(10), 496; https://doi.org/10.3390/toxins17100496 - 6 Oct 2025
Viewed by 1126
Abstract
The puff adder (Bitis arietans) is a clinically relevant viper species found throughout Africa, and it is responsible for a greater incidence of health-related envenomations than all other snake species on the continent combined. Unresolved skeletal muscle damage is a common [...] Read more.
The puff adder (Bitis arietans) is a clinically relevant viper species found throughout Africa, and it is responsible for a greater incidence of health-related envenomations than all other snake species on the continent combined. Unresolved skeletal muscle damage is a common consequence of B. arietans envenomation that can result in long-term morbidity and even death. Antivenom treatment can mitigate the systemic effects of the venom but offers little protection against local tissue damage. Identifying the mechanisms through which B. arietans venom induces tissue damage and impedes skeletal muscle regeneration could identify possible treatment alternatives that could help alleviate the long-term consequences of envenomation. Skeletal muscle has an innate ability to regenerate, but constituents within the venom can impede multiple stages of this regeneration process. In this study, we employed a combination of biochemical analyses, cell-based assays, and in vivo experiments to assess the toxicological implications of B. arietans envenomation and its impacts on key processes of regeneration. Our findings demonstrate that the pathological characteristics of permanent muscle damage resulting from B. arietans envenomation may be attributed to the venom’s effects on muscle stem cell precursors, the extracellular matrix (ECM), and the influence of blood-borne proteins that promote fibrosis. Full article
(This article belongs to the Special Issue Snake Bite and Related Injury)
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21 pages, 4001 KB  
Article
Exploring the Venom Diversity of Australian Taipans: Comparative Characterization of Oxyuranus microlepidotus and Oxyuranus scutellatus
by Guilherme Gonelli Paz, Patrick Jack Spencer, Daniel Carvalho Pimenta and Emidio Beraldo-Neto
Toxins 2025, 17(10), 488; https://doi.org/10.3390/toxins17100488 - 1 Oct 2025
Viewed by 1838
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Animal Venoms: Unraveling the Molecular Complexity (2nd Edition))
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20 pages, 4713 KB  
Article
X Marks the Clot: Evolutionary and Clinical Implications of Divergences in Procoagulant Australian Elapid Snake Venoms
by Holly Morecroft, Christina N. Zdenek, Abhinandan Chowdhury, Nathan Dunstan, Chris Hay and Bryan G. Fry
Toxins 2025, 17(8), 417; https://doi.org/10.3390/toxins17080417 - 18 Aug 2025
Cited by 1 | Viewed by 5930
Abstract
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: [...] Read more.
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
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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19 pages, 2689 KB  
Review
Mapping Evidence on the Regulations Affecting the Accessibility, Availability, and Management of Snake Antivenom Globally: A Scoping Review
by Ramsha Majeed, Janette Bester, Kabelo Kgarosi and Morné Strydom
Trop. Med. Infect. Dis. 2025, 10(8), 228; https://doi.org/10.3390/tropicalmed10080228 - 14 Aug 2025
Cited by 1 | Viewed by 2751 | Correction
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Recent Advances in Snakebite Envenoming Research)
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18 pages, 1147 KB  
Article
Geographic Variation in Venom Proteome and Toxicity Profiles of Chinese Naja atra: Implications for Antivenom Optimization
by Jianqi Zhao, Xiao Shi, Guangyao Liu, Yang Yang and Chunhong Huang
Toxins 2025, 17(8), 404; https://doi.org/10.3390/toxins17080404 - 12 Aug 2025
Cited by 1 | Viewed by 1580
Abstract
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. [...] Read more.
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
(This article belongs to the Special Issue Animal Venoms: Unraveling the Molecular Complexity (2nd Edition))
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Article
Coffea arabica Extracts and Metabolites with Potential Inhibitory Activity of the Major Enzymes in Bothrops asper Venom
by Erika Páez, Yeisson Galvis-Pérez, Jaime Andrés Pereañez, Lina María Preciado and Isabel Cristina Henao-Castañeda
Pharmaceuticals 2025, 18(8), 1151; https://doi.org/10.3390/ph18081151 - 1 Aug 2025
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Abstract
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 [...] Read more.
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 (PLA2s). 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
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