RARE DISEASE
Scorpion envenomation
Scorpion envenomation
Scorpion envenomation
Drug discovery
1
drug
With orphan designation
Overview
Scorpion envenomation causes localized pain and systemic effects (autonomic dysfunction, cardiopulmonary instability, neuromuscular hyperactivity) mediated by neurotoxins, primarily affecting sodium channels [1][5][11]. Severe cases may lead to Takotsubo cardiomyopathy, pulmonary edema, or shock [1][4]. Antivenom is effective against New World species (e.g., Centruroides), while Old World envenomations require intensive symptomatic management [1][3][9]. Mortality remains rare (<1% with treatment) but disproportionately impacts children [2][7][19].
Therapies
Antivenom: First-line for severe envenomation in Americas (F(ab')₂ fragments) [3][4][9]
Supportive care: Prazosin for hypertension, benzodiazepines for neuromuscular symptoms, mechanical ventilation for pulmonary edema [6][9][16]
Avoid: Corticosteroids, antihistamines, and diuretics (exacerbate cardiovascular instability) [6][9][13]
Categories: rare disorders due to toxic effects
Research Papers
992 drug discovery papers about Scorpion envenomation, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
992 drug discovery papers about Scorpion envenomation, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-30 | Dexmedetomidine versus Clonidine as Intrathecal Adjuvants to Hyperbaric Ropivacaine for Subarachnoid Block in Patients with History of Scorpion Bite undergoing Infraumbilical Surgery: A Double-blinded Randomised Clinical Study
Introduction: Patients with previous scorpion sting may show variable response to spinal local anaesthetics because scorpion toxins can alter voltage-gated sodium-channel behaviour. Ropivacaine and intrathecal alpha-2 agonists may improve block reliability in this subgroup. Aim: To compare intrathecal dexmedetomidine and clonidine as adjuvants to 0.75% hyperbaric ropivacaine for Subarachnoid Block (SAB) in patients with history of scorpion bite undergoing infraumbilical surgery. Materials and Methods: This double-blinded randomised clinical study was conducted in the Department of Anaesthesiology, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, Maharashtra, India. The study included 78 American Society of Anaesthesiologists (ASA) I-II adults aged 18-60 years with documented scorpion bite history scheduled for elective infraumbilical surgery. Patients were allocated equally. Group RD received 3 mL 0.75% hyperbaric ropivacaine with dexmedetomidine 5 µg intrathecally, while Group RC received 3 mL 0.75% hyperbaric ropivacaine with clonidine 30 µg. Block characteristics, block success and haemodynamic variables were recorded. Normality was assessed using the Shapiro-Wilk test. Continuous variables were compared using the independentsamples t-test, and categorical variables using the Chi-square or Fisher’s exact test. A p-value <0.05 was considered significant. Results: A total of 78 patients were randomised, with 39 patients allocated to each group. Baseline characteristics were comparable between Group RD and Group RC, including age (42.6±9.8 vs 43.9±10.2 years), sex distribution (21/18 vs 23/16 male/female), weight (63.4±8.1 vs 64.1±7.6 kg), height (162.8±6.9 vs 163.2±7.1 cm), baseline heart rate (78.4±7.0 vs 79.5±6.8 beats/min), baseline mean arterial pressure (94.8±5.9 vs 93.7±6.1 mmHg), and duration of surgery (73.4±15.2 vs 75.1±14.8 minutes). Among patients with successful measurable block, sensory onset was significantly faster in Group RD than in Group RC (3.5±0.9 vs 5.3±1.3 minutes; p-value <0.001), and motor onset was also earlier (4.3±0.9 vs 5.7±1.2 minutes; p-value <0.001). Group RD demonstrated a longer duration of sensory block (274.2±24.9 vs 228.8±23.7 minutes; p-value <0.001) and motor block (245.8±28.0 vs 196.7±23.4 minutes; p-value <0.001). Successful spinal block was achieved in 38/39 (97.4%) patients in Group RD and 36/39 (92.3%) patients in Group RC; however, the difference was not statistically significant (p-value=0.615). Conclusion: Intrathecal dexmedetomidine added to 0.75% hyperbaric ropivacaine produced faster sensory and motor onset and prolonged block duration compared with clonidine in patients with previous scorpion bite. Both regimens were haemodynamically acceptable, but dexmedetomidine showed superior overall block characteristics and reliability
2026-08-08 | Comprehensive Ayurvedic Management of a Post-Scorpion Envenomation Ulcer: A Case Report
Scorpion envenomation is a common medical emergency in rural regions and may present with manifestations ranging from localized pain to systemic complications. Delayed presentation, inadequate wound care, or poor adherence to treatment may contribute to secondary infection, delayed healing, and post-envenomation ulcer formation. This case report describes the successful management of a post-scorpion envenomation ulcer in a 62-year-old male who presented with pain, swelling, and purulent discharge over the right great toe one week after a scorpion sting. The patient initially relied on home remedies and sought medical attention two days after the sting. Inconsistent adherence to prescribed treatment, dietary recommendations (Pathya-Apathya), and follow-up was associated with progression of the local lesion. Based on Ayurvedic clinical assessment, the condition was interpreted as Vishaja Vrana. The patient was subsequently managed with an individualized Ayurvedic treatment regimen comprising internal medications, local wound care, and dietary and lifestyle modifications in accordance with the principles of Visha Chikitsa and Vrana Chikitsa. Progressive reduction in pain, local inflammation, and purulent discharge, along with satisfactory wound healing, was observed during follow-up, culminating in complete ulcer healing. According to Ayurvedic principles, the prescribed interventions are traditionally indicated for the management of Visha-related disorders and wound healing. However, as this is a single case report, a direct therapeutic effect or venom-neutralizing activity cannot be established. Further well-designed clinical studies are warranted to evaluate the safety and efficacy of these Ayurvedic interventions in the management of post-scorpion envenomation ulcers.
2026-07-01 | Management Of Scorpion Bite Through Ayurveda: A Case Report
Agadatantra, the branch of toxicology in Ayurveda, refers to various methods of eliminating toxins from the body that arises from animate, inanimate, and artificial poisons. Scorpion stings are a serious health concern in rural areas. In Agadatantra, the symptoms of scorpion sting are explained under Vrischika visha (~scorpion venom poisoning). The main characteristics of scorpion venom poisoning are Vahnivat dahanam (~burning sensation like fire), Kshipram urdhvarohanam (~quick spreading in an upward direction), Danshe ruja tishthati (~pain remains at bite site), Sadyah ati ruk (~instant severe pain), Danshashyavata (~brownish discoloration of bite site), and Dansha toda (~ pricking type of pain at bite site). This is a case report of a 34- year- old male, who had an episode of Vrischika damsha (~scorpion bite) and presented to the outpatient department with complaints of severe edema, pain and redness, and itching. The first line of management for scorpion stings is typically symptomatic including strong analgesics, which can be systemic (opiates or paracetamol) or localized (such as a cold compress). In Ayurveda classics, Hinguadi gulika is one of the formulations mentioned in Vrischikavisha prakarana, which has been referred to as the most potent Lepana (~anointment) for scorpion venom poisoning. In comparison to existing conventional treatment modalities, Hinguadi gulika lepana is a very simple and very cost- effective procedure. Hinguadi gulika was given in combination with Kulakadi kashaya which is widely practiced in all Visha (~poison) conditions. In the present case, Hinguadi gulika and Kulakadi kashayam have shown assuring results in the management of acute scorpion envenomation.
2026-06-30 | Long-term trends in urban scorpionism under mechanical and chemical control in a Brazilian municipality
Urban scorpionism is a persistent public health challenge in medium-sized Brazilian cities. While mechanical capture is routinely employed for surveillance, chemical control was reintroduced in November 2019 to intensify interventions in high-risk microenvironments. We conducted a longitudinal observational study using monthly aggregated data (January 2014–December 2024). Interrupted time-series analysis with segmented regression was used to evaluate temporal trends, seasonality and post-intervention changes. Mechanical capture intensity was included with 0-, 3- and 6-month lags. Robust standard errors were calculated using Newey–West corrections. Scorpion sting accidents remained present year-round, with predictable seasonal peaks despite sustained mechanical control. Lagged capture analyses showed no significant association with accident counts, indicating that captures primarily reflect operational effort. The November 2019 introduction of targeted chemical control was associated with an immediate level reduction of − 7.40 accidents (95% CI −13.73 to − 1.07; p = 0.022) and a significant negative change in slope (− 0.277 accidents/month; 95% CI −0.445 to − 0.110; p = 0.001). Comparison with the counterfactual projection showed divergence between observed and expected trajectories, corresponding to an estimated cumulative difference of 1,001 cases between November 2019 and December 2024 (30.9% reduction relative to the expected continuation of the pre-intervention trend). Integrated mechanical and focal chemical control were associated, in segmented regression analyses, with reductions in both level and slope of scorpion sting incidence after 2019, consistent with attenuation of the previously observed upward trend without evidence of abrupt disruption of seasonal dynamics. Surveillance indicators reflect sustained operational activity, while chemical interventions may contribute to targeted risk reduction within persistently affected urban settings.
2026-03-24 | Integrating Traditional Knowledge in Emergency Medicine: The Role of Heat Application in Scorpion Stings
Objective: This study aims to evaluate the effects of pre-hospital hot and cold applications on analgesic requirements and symptom severity in scorpion envenomation, with the broader goal of integrating traditional practices into modern emergency care.Methods: This retrospective descriptive study included 229 adult patients who presented to Muğla Training and Research Hospital with scorpion stings between January 1, 2021, and December 31, 2022. Patients were categorized into three groups based on pre-hospital interventions: hot application (n=46), cold application (n=100), and no intervention (n=83). Clinical stage, pain intensity (VAS), analgesic use, and demographic characteristics were compared.Results: Most patients (97.8%) were classified as stage 1 envenomation. The need for NSAIDs (19.3%) and opioids (1.5%) was significantly lower in the hot application group (p
proteins
2026-06-10 | COMPONENTS AND DIAGNOSIS OF SCORPIO NVENOM AND MEDICAL IMPORTANT
Thisreview presents both the detrimental and beneficial properties of scorpion venom toxinsand discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.
2026-02-26 | Stinging Salvation: Harnessing Scorpion Venom Peptides for Revolutionary Pain Relief
from the Buthidae family, show real promise as painkillers that skip opioids altogether. They work by hitting specific ion channels and dialing down inflammation. This review gathers information on their molecular setups: disulfide-bridged types and those without, weighing in at 3 to 10 kilodaltons (kDa). Structural features include motifs stabilized by cysteines. In pain signaling, they block voltage-gated sodium channels (NaV) such as NaV1.7 and NaV1.8; take the BmK analgesic-antitumor peptide (BmK-AGAP) for example. Additionally, scorpion venom heat-resistant peptide (SVHRP) reduces microglia activity. Tests on rodents using formalin injections, acetic acid writhing, and chronic constriction injury (CCI) setups reveal pain relief that depends on dose and stacks up to morphine. Pairings like AGAP with lidocaine decrease the effective dose by half. In terms of safety, therapeutic levels have low-toxicity with a median lethal dose (LD50) over 20 mg/kg. Issues crop up with immune responses, unintended targets, and differences in venom batches. Clinical information remains thin, so gaps persist. Engineered versions could change the game for neuropathic pain, inflammatory conditions, and cancer-related discomfort. Standardization plus Phase I studies would help move this forward.
2026-02-16 | From venom peptides to neurotherapeutics: BmK defensins and short-chain peptides as modulators of ion channels.
Scorpions, having inhabited the Earth long before the emergence of humans, represent an ancient lineage of arthropods. While often regarded with fear due to their potential to induce severe pain or fatal envenomation, scorpion venoms constitute complex cocktails of bioactive molecules known as toxins. Notably, these toxic components have been repurposed in medical research as valuable sources for therapeutic development. In traditional Chinese medicine (TCM), the venom of Buthus martensii Karsch (BmK), commonly referred to as the Chinese scorpion, has been historically employed in the treatment of various neurological disorders, including epilepsy, stroke, glioma, and pain. The principal bioactive constituents of BmK venom are polypeptides that selectively target membrane ion channels. Among these, defensins and short-chain toxins (28-40 amino acids in length) have been identified as key modulators of potassium channels, TRP channels, and chloride channels. These short-chain peptides exhibit several distinct pharmacological advantages, including efficient tissue penetration due to their low molecular mass, remarkable target specificity for particular ion channel isoforms or states, inherently low immunogenicity, and considerable structural versatility that facilitates engineering (e.g., fusion strategies, point mutations) to optimize pharmacokinetics and pharmacodynamics. As such, they represent promising molecular scaffolds for drug design aimed at addressing unmet clinical needs in neurology. We summarize the most advanced drug candidates derived from BmK defensins and short-chain toxins, which exhibit activity against Kv1.3, BK, TRPV1, and other channels implicated in epilepsy, neuroinflammation, glioma, and pain. Structural and functional insights into these peptides reveal mechanisms underlying their target specificity and pharmacological advantages, such as blood-brain barrier penetration and low immunogenicity. This review underscores the originality of BmK peptides as molecular tools and lead compounds for next-generation neurology therapeutics, providing a focused resource for researchers in ion channel pharmacology and peptide-based drug design.
2026-01-18 | The Rami Five-Checkpoint Framework for AI-Guided mRNA-Encoded Neutralizers: A Unified Computational Platform for Snake and Scorpion Venom Antidote Design
Envenomation from venomous snakes and scorpions remains a major global health challenge, disproportionately affecting populations in low-resource settings where access to conventional antivenoms is limited by cost, cold-chain requirements, and species specificity. This work introduces the Rami Five-Checkpoint Framework, a unified computational methodology for the design of mRNA-encoded neutralizing proteins targeting venom toxins. The framework integrates five sequential design checkpoints: (1) toxin target selection and lethality scoring, (2) human codon optimization of mRNA sequences, (3) RNA secondary structure validation, (4) immunogenicity and toxin-binding prediction, and (5) economic feasibility assessment. The approach is demonstrated through parallel in silico case studies targeting two mechanistically distinct toxins: beta-taipoxin from the Inland Taipan (Oxyuranus microlepidotus) and the CsEv5 alpha-toxin from the Arizona bark scorpion (Centruroides sculpturatus). AI-guided de novo neutralizer designs exhibited predicted nanomolar binding affinities, high thermostability, favorable mRNA expression characteristics, and broad HLA population coverage. Cost modeling suggests the potential for substantial reductions in production cost relative to traditional animal-derived antivenoms. This study is exclusively computational and does not include experimental protocols, toxin synthesis, or clinical procedures. The framework is intended as a reusable design-time platform to accelerate antivenom research, support future experimental validation, and advance next-generation therapeutic strategies for envenomation preparedness.
2025-12-13 | Enzymatic characterization and proteomic profiling of venoms from the medically important Androctonus species.
Egyptian scorpions of the Androctonus genus (family Buthidae) produce life-threatening stings owing to their neurotoxic venom. However, the composition and enzymatic activities of their venoms remain poorly understood: We used electrophoresis to analyze the protein components of venoms collected from three Androctonus species: Androctonus amoreuxi, Androctonus australis, and Androctonus bicolor. Mass spectrometric analysis was performed to characterize the peptides present in these venoms. The phospholipase A2 (PLA2), hyaluronidase, and protease activities of the venoms were examined to gauge their potential contribution to venom toxicity. Finally, the antibacterial and hemolytic activities of the venoms were evaluated. The electrophoretic profiles of the three venoms showed features specific to each species, with distinct protein bands observed at 75, 74, 67, 48, 46, 40, and 28 kDa, along with a notable band above the 15-kDa mark. Liquid chromatography/mass spectrometry analyses were used to detect the presence of 369, 324, and 351 components in with molecular masses in the range of 500-10,000 Da in the venoms of A. amoreuxi, A. australis, and A. bicolor, respectively. Disulfide-rich peptides (three disulfide bridges) were abundant, but peptides without disulfide bonds were also detected in all venom samples. All three venoms exhibited hyaluronidase activities, whereas protease and PLA2 activities were either weak (at 1 µg and 10 µg) or undetectable, even at higher concentrations (up to 20 µg). All assays were performed using venoms standardized by dry weight to ensure consistent protein quantities. Crude venoms of A. amoreuxi and A. australis showed antibacterial activity against E. coli and B. subtilis (5-10 μg), whereas A. bicolor required 10 μg. Hydrophobic fractions (40-55 min) of A. australis alone retained this activity. This work furthers our knowledge of the enzymatic and peptide composition of Androctonus venoms, unveiling their potential in drug delivery enhancement and other biomedical applications. These findings will inform the development of better strategies for the treatment and prevention of scorpion envenomation.
vaccines
2024-09-30 | 21st century Latin American synthetic peptides for their application in antivenom production
Envenomation caused by snakes, scorpions, and spiders represents a serious public health problem in Latin America. The antivenoms used for its treatment are produced by immunizing horses repeatedly with sublethal doses of animal venoms along with the adjuvant. However, venom availability is a bottleneck. Furthermore, toxin-neutralizing antibodies are only a few of the total produced with this classical method. Therefore, high doses of antivenom are required to achieve the neutralization power, which usually causes adverse reactions in the patient. With the aim of obtaining a higher proportion of toxin-neutralizing antibodies while reducing the dependency on venom availability, alternative immunization protocols have been explored using synthetic peptides with epitopes from clinically relevant toxins. The process to design an immunogenic peptide entitles: (a) choice of the medical relevant toxins in the venom; (b) identification of the epitopes in the selected toxins; (c) improvement of peptide immunogenicity; (d) immunogen synthesis; and e) in vitro and in vivo evaluation. The present article aims to review the advances in the design of immunogenic synthetic peptides for their application in antivenom production in Latin America during the 21st century. Epitopes have been identified from many clinically important toxins in Latin American snakes (snake venom metalloproteinases, snake venom serine proteases, crotamine, phospholipases A2, and three-finger toxins), scorpions (beta-mammal/insect toxin Ts1, alpha-mammal toxin Ts2, alpha-mammal toxin Ts3, toxin Ts4, and beta-mammal Tt1g neurotoxin), and spiders (dermonecrotic toxin and delta-ctenitoxin-Pn2a). Nevertheless, their application is still experimental, even though they are ideal for large-scale and low-cost antivenom production, factors that are necessary to meet national and regional demands.
2024-05-25 | Evaluation of the immunoprotective power of a multiple antigenic peptide against Aah II toxin of Androctonus australis hector scorpion
Scorpion envenoming (SE) is a public health problem in developing countries. In Algeria, the population exposed to the risk of SE was estimated at 86.45% in 2019. Thus, the development of a vaccine to protect the exposed population against scorpion toxins would be a major advance in the fight against this disease. This work aimed to evaluate the immunoprotective effect of a Multiple Antigenic Peptide against the Aah II toxin of Androctonus australis hector scorpion, the most dangerous scorpion species in Algeria. The immunogen MAP1Aah2 was designed and tested accordingly. This molecule contains a B epitope, derived from Aah II toxin, linked by a spacer to a universal T epitope, derived from the tetanus toxin. The results showed that MAP1Aah2 was non-toxic despite the fact that its sequence was derived from Aah II toxin. The immunoenzymatic assay revealed that the 3 immunization regimens tested generated specific anti-MAP1Aah2 antibodies and cross-reacted with the toxin. Mice immunized with this immunogen were partially protected against mortality caused by challenge doses of 2 and 3 LD50 of the toxin. The survival rate and developed symptoms varied depending on the adjuvant and the challenge dose used. In the in vitro neutralization test, the immune sera of mice having received the immunogen with incomplete Freund's adjuvant neutralized a challenge dose of 2 LD50. Hence, the concept of using peptide dendrimers, based on linear epitopes of scorpion toxins, as immunogens against the parent toxin was established. However, the protective properties of the tested immunogen require further optimizations.
2022-01-24 | Long-term antibody response and protective effect induced by attenuated scorpion toxins: Involvement of memory plasma cells.
In Algeria, Androctonus australis hector scorpion envenomation remains a major problem of public health because of non-efficient therapy. The development of safe vaccine against scorpion venom could be one key strategy for the envenomation prevention. The irradiation of venom by γ-rays develops suitable immunogens which produced effective antivenom and safe vaccine. In this study, we investigated the ability of the irradiated toxic fraction (γ-FtoxG50) to induce long-term memory humoral response in immunized animals (mice and rabbits), by involving the long-lived plasma cells to prevent efficiently the lethality of scorpion envenomation. For this purpose, an appropriate immunization schedule was established in mice and rabbits using three (3) similar doses of γ-FtoxG50 associated with Alum adjuvant. Obtained results indicate that the long-term immunogenicity of γ-FtoxG50 is able to induce the long-term memory humoral response with a high level of specific antibodies. The long-term persistence of antibody levels could depend on bone marrow memory plasma cells. These cells produce continuously antibodies without antigen stimulus. Furthermore, an enhanced memory response was obtained post-repeated envenomation with toxic native venom that leads to improved protection of animals. Together, pre-existing protective antibodies and the activation of memory B-cells could induce a rapid neutralization of scorpion toxins and long-term protection against scorpion envenomation.
2022-01-20 | Strategies for Heterologous Expression, Synthesis, and Purification of Animal Venom Toxins
Animal venoms are complex mixtures containing peptides and proteins known as toxins, which are responsible for the deleterious effect of envenomations. Across the animal Kingdom, toxin diversity is enormous, and the ability to understand the biochemical mechanisms governing toxicity is not only relevant for the development of better envenomation therapies, but also for exploiting toxin bioactivities for therapeutic or biotechnological purposes. Most of toxinology research has relied on obtaining the toxins from crude venoms; however, some toxins are difficult to obtain because the venomous animal is endangered, does not thrive in captivity, produces only a small amount of venom, is difficult to milk, or only produces low amounts of the toxin of interest. Heterologous expression of toxins enables the production of sufficient amounts to unlock the biotechnological potential of these bioactive proteins. Moreover, heterologous expression ensures homogeneity, avoids cross-contamination with other venom components, and circumvents the use of crude venom. Heterologous expression is also not only restricted to natural toxins, but allows for the design of toxins with special properties or can take advantage of the increasing amount of transcriptomics and genomics data, enabling the expression of dormant toxin genes. The main challenge when producing toxins is obtaining properly folded proteins with a correct disulfide pattern that ensures the activity of the toxin of interest. This review presents the strategies that can be used to express toxins in bacteria, yeast, insect cells, or mammalian cells, as well as synthetic approaches that do not involve cells, such as cell-free biosynthesis and peptide synthesis. This is accompanied by an overview of the main advantages and drawbacks of these different systems for producing toxins, as well as a discussion of the biosafety considerations that need to be made when working with highly bioactive proteins.
2018-04-23 | Safety and efficiency of active immunization with detoxified antigen against scorpion venom: side effect evaluation.
The efficiency and safety of vaccine are the most important properties, however, as any medication, it can induce side effects. This prophylactic therapy could be used to prevent the lethal and pathophysiological effects induced after scorpion envenomation. In this study, detoxified venom associated to alum adjuvant (V*alum) is used as a vaccine against scorpion venom for immunization of mice. We evaluate the safety and the inflammatory response of this vaccine. We also investigated the protective effect of this formulation against the toxicity of native Androctonus australis hector venom. Results showed no adverse events occurred after immunization of animals. This active immunization of animals did not cause change in vascular permeability, no edema formation in the studied organs. Furthermore, there are no IgE production in sera, nor change in the morphology of the mast cells in skin tissues. However, low inflammatory response triggered by activating the recruitment of eosinophils associated to IL-4 and IL-5 release was observed. All immunized animals are protected from the toxic effects of native venom until 6 LD50 and to 7 LD50 after the second challenge. This safe vaccine preparation seems to induce a long-term protection without any risk of deleterious inflammatory response.
antibodies
2026-09-23 | Histomorphometric changes in the bronchi and lung parenchyma of rats one day after administration of venom from the scorpion Leiurus macroctenus
The lungs are one of the target organs affected by scorpion venom. Given the expansion of scorpion distribution ranges and climate change, the likelihood of venomous scorpions appearing in new territories inhabited by humans is increasing. Thus, there is a need for an in-depth morphological study of the delayed outcomes of envenomation by medically significant scorpion species. The aim of the study was to determine histological and micromorphometric changes in the bronchi and lung parenchyma of rats 1 day after administration of Leiurus macroctenus scorpion venom. The experiment involved 10 male Wistar laboratory rats maintained under vivarium conditions and divided into 2 groups: group 1 – control rats (n=5), which received physiological saline, and group 2 – rats which received scorpion venom at a dose of 28,8 μg/ml (n=5). One day after administration of Leiurus macroctenus scorpion venom, the rats were euthanized, lung samples were removed and subsequently fixed in 10 % neutral formalin or 2.5 % glutaraldehyde and 1 % osmium tetroxide, followed by standard embedding in paraffin or an epoxy resin mixture. For histological and morphometric examination of the lungs, sections with a thickness of 4-5 μm were prepared according to a standard method, followed by staining with hematoxylin-eosin and by the Azan Trichrome, as well as semithin sections with a thickness of 1-2 μm followed by methylene blue staining. Microscopy of the obtained specimens was performed using an OLIMPUS BX 41 at magnifications from ×40 to ×1000. Morphometric analysis (alveolar width, alveolar entrance width and alveolar depth, interalveolar septum thickness, and width of the conducting portion of the bronchiole) was performed using the software Quickphoto Micro 2.3. Statistical analysis was performed using the licensed software package “Statistica 6.0” using nonparametric evaluation methods. One day after administration of Leiurus macroctenus scorpion venom, pronounced degenerative-destructive changes were found in the lungs of rats, manifested by areas of interalveolar septal destruction, formation of areas of increased air content, hemorrhages, areas of dys- and atelectasis, foci of interstitial and intra-alveolar edema, and destruction of alveolocytes with the formation of cavities in which tissue detritus accumulated. Against this background, most sections showed an inflammatory reaction with marked interstitial, peribronchial and peribronchiolar infiltration by white blood cells. The bronchioles showed epithelial desquamation, thickening of the muscular layer and narrowing of the lumen, enlargement of the mucous glands and accumulation of mucus in them. Statistical analysis of morphometric parameters showed a significant decrease in alveolar width by 36.84 % (p=0.0032), alveolar entrance width by 40.52 % (p=0.0003), alveolar depth by 23.02 % (p=0.0140), and the width of the conducting portion of the respiratory bronchiole by 22.26 % (p=0.0003) compared with the control group. At the same time, the mean interalveolar septum thickness increased by 20.20 % (p=0.0065). The ratio of alveolar entrance width to alveolar depth and the ratio of the width of the conducting portion of the respiratory bronchiole to alveolar depth did not differ significantly from the control group values. Thus, Leiurus macroctenus venom causes pronounced acute complex lung injury after 1 day, manifested by a combination of alveolar destruction, edematous, hemodynamic and inflammatory changes, and impaired bronchial patency.
2026-07-20 | Scorpion envenomation in pregnancy: clinical symptoms, maternal and fetal outcomes and management strategies.
Scorpion stings pose a significant public health threat, particularly in developing regions, leading to considerable morbidity and mortality. This systematic review assesses the clinical manifestations, maternal and fetal outcomes, and evaluates the treatment approaches in pregnant women affected by scorpion stings. A systematic search was conducted in multiple databases (Web of Science, PubMed, Scopus, SID, and Magiran) from inception to October 26, 2024. Case reports, case series, and observational studies with accessible full texts were included based on predefined eligibility criteria. Data extraction included study characteristics, maternal and gestational age, scorpion species, symptoms, and pregnancy outcomes. The methodological quality of included studies was assessed independently by two reviewers using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and NIH (National Institutes of Health) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Disagreements were resolved by consensus or consultation with a third reviewer. A total of 14 studies were included in the review, comprising case reports and case series from various countries. The average maternal age was 27.14 years, and gestational age averaged 23.94 weeks. Common symptoms reported included localized pain (71.4%), nausea (14.3%), vomiting (14.3%), fever (14.3%), and abnormal vital signs (7.1%) in severe cases. The majority of studies (78.6%) indicated low symptom severity. Maternal and fetal outcomes were generally favorable, although severe outcomes, such as maternal death and intrauterine fetal death, were reported in a few cases. Antivenom was administered in only four cases (28.6%) indicating a potential gap in its use. Scorpion envenomation during pregnancy typically presents with localized pain, while severe systemic symptoms are less common. Although most maternal and fetal outcomes are favorable, serious complications such as maternal or intrauterine fetal death can occur. These findings suggest that antivenom may be underutilized in pregnant women. Therefore, we recommend: (1) increased vigilance for severe symptoms, especially abnormal vital signs; (2) timely antivenom administration in moderate-to-severe cases; and (3) standardized reporting of pregnancy-specific outcomes. Large prospective studies are urgently needed to establish evidence-based management guidelines.
2026-06-24 | Scorpionism in the Amazon: Evidence, Challenges and Actions for Controlling a Neglected Disease.
Scorpion sting envenomations impose an increasing burden in the Amazon and result in a considerable impact on public health. The genus Tityus accounts for nearly all clinically relevant cases, with T. metuendus, T. silvestris and T. obscurus being responsible for most of envenomations in the region. In the state of Amazonas, Manaus and Apuí account for most of cases reported, with an evident expansion to other regions, including the Solimões River region and the Upper Negro River region, where most of the exposed population is found in Indigenous and riverine communities. The increasing burden and high severity rates of scorpion stings in the Amazon may result from the capacity of adaptation of the endemic species to the environmental changes and limitations in providing adequate healthcare to patients. The clinical profile of patients stung by different species has similar local and systemic manifestations. In Manaus, T. metuendus is the species that is most commonly responsible for severe cases observed in children, due to them presenting circulatory collapse and acute respiratory distress, while T. apiacas and T. silvestris present systemic neurological manifestations, characterized by generalized muscle spasms described as the sensation of receiving an electric shock, apparently not reversed by the available antivenom. Scorpionism in the Amazon combines the biological complexity and variability of Tityus species and their venoms, social and environmental determinants and healthcare challenges. These features require solutions of interinstitutional, interdisciplinary networks that are capable of integrating biology, venomics, clinical medicine, public health, environmental sciences and the social sciences.
2026-04-04 | Pediatric scorpion envenomation in Tunisia: epidemiology, clinical features, therapeutic management and outcomes in a 14-year cohort study
Background Scorpion envenomation is a persistent public health concern in Tunisia, particularly in rural areas. Children are especially vulnerable due to low body weight and immature physiological systems. Methods We conducted a retrospective cohort study over a 14-year period (2011–2024) in the Pediatric Intensive Care Unit of Hedi Chaker University Hospital, Sfax, Tunisia. Children aged 0–14 years with confirmed scorpion envenomation were included. Epidemiological, clinical, biological, and outcome data were analyzed. Results Sixty-nine children were included, with a mean age of 4.6 years; two-thirds were under five years of age. Most cases occurred during summer and originated from rural areas. Systemic manifestations were present in 85.5% of patients. Moderate and severe envenomation were predominant, with 49.3% classified as Grade II and 39.1% as Grade III. Cardiac involvement was frequent, with elevated cardiac troponin observed in nearly half of cases and left ventricular dysfunction in more than one-third. Antivenom was administered in 88.4% of patients, and inotropic support was required in 25.9%. There were no fatalities; however, 18.5% of patients developed sequelae, mainly cardiac. Younger age, severe clinical presentation, seizures, respiratory distress, hyperglycemia, ventricular dysfunction, pulmonary edema, and delayed medical care (>2 hours) were significantly associated with adverse outcomes. Conclusion Pediatric scorpion envenomation often leads to systemic and cardiac complications. Early recognition and rapid management are critical to reducing morbidity.
2026-04-02 | Indian lone commercial antivenom against Indian red scorpion venom demonstrates limited immunorecognition and partial neutralisation of enzymatic, pharmacological, and some toxic effects of Heterometrus bengalensis (Indian black scorpion) venom proteins in vitro and in vivo.
Scorpion envenomation remains a significant yet under-addressed public health issue in India. Heterometrus bengalensis (HB), a medically important scorpion, can induce clinically relevant local and systemic toxicity. However, limited research has evaluated the immunological recognition and neutralisation efficacy of existing commercial anti-scorpion antivenoms (ASV) against HB venom (HBV). This study evaluated the immunological cross-reactivity and neutralisation potential of a commercial ASV against HBV using in vitro and in vivo approaches. Immunochemical assays (enzyme-linked immunosorbent assay and Western blotting) demonstrated partial immunoreactivity toward HBV proteins in the range of ~75-37 kDa, but exhibited poor recognition of low-molecular-mass proteins (<20 kDa). ASV showed feeble neutralisation of HBV enzymatic activities, HBV toxicity, and reactive oxygen species (ROS) production in Caenorhabditis elegans. ASV also showed poor protective efficacy against HBV-induced local and systemic toxicity in Swiss albino mice. ASV also failed to attenuate the HBV-induced production of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in mice. Therefore, this study highlights insufficient immunological coverage and underscores the need for species-specific antivenoms. The findings provide crucial insights for enhancing therapeutic interventions for scorpion envenomation in India.
small molecules
2026-08-30 | Dexmedetomidine versus Clonidine as Intrathecal Adjuvants to Hyperbaric Ropivacaine for Subarachnoid Block in Patients with History of Scorpion Bite undergoing Infraumbilical Surgery: A Double-blinded Randomised Clinical Study
Introduction: Patients with previous scorpion sting may show variable response to spinal local anaesthetics because scorpion toxins can alter voltage-gated sodium-channel behaviour. Ropivacaine and intrathecal alpha-2 agonists may improve block reliability in this subgroup. Aim: To compare intrathecal dexmedetomidine and clonidine as adjuvants to 0.75% hyperbaric ropivacaine for Subarachnoid Block (SAB) in patients with history of scorpion bite undergoing infraumbilical surgery. Materials and Methods: This double-blinded randomised clinical study was conducted in the Department of Anaesthesiology, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, Maharashtra, India. The study included 78 American Society of Anaesthesiologists (ASA) I-II adults aged 18-60 years with documented scorpion bite history scheduled for elective infraumbilical surgery. Patients were allocated equally. Group RD received 3 mL 0.75% hyperbaric ropivacaine with dexmedetomidine 5 µg intrathecally, while Group RC received 3 mL 0.75% hyperbaric ropivacaine with clonidine 30 µg. Block characteristics, block success and haemodynamic variables were recorded. Normality was assessed using the Shapiro-Wilk test. Continuous variables were compared using the independentsamples t-test, and categorical variables using the Chi-square or Fisher’s exact test. A p-value <0.05 was considered significant. Results: A total of 78 patients were randomised, with 39 patients allocated to each group. Baseline characteristics were comparable between Group RD and Group RC, including age (42.6±9.8 vs 43.9±10.2 years), sex distribution (21/18 vs 23/16 male/female), weight (63.4±8.1 vs 64.1±7.6 kg), height (162.8±6.9 vs 163.2±7.1 cm), baseline heart rate (78.4±7.0 vs 79.5±6.8 beats/min), baseline mean arterial pressure (94.8±5.9 vs 93.7±6.1 mmHg), and duration of surgery (73.4±15.2 vs 75.1±14.8 minutes). Among patients with successful measurable block, sensory onset was significantly faster in Group RD than in Group RC (3.5±0.9 vs 5.3±1.3 minutes; p-value <0.001), and motor onset was also earlier (4.3±0.9 vs 5.7±1.2 minutes; p-value <0.001). Group RD demonstrated a longer duration of sensory block (274.2±24.9 vs 228.8±23.7 minutes; p-value <0.001) and motor block (245.8±28.0 vs 196.7±23.4 minutes; p-value <0.001). Successful spinal block was achieved in 38/39 (97.4%) patients in Group RD and 36/39 (92.3%) patients in Group RC; however, the difference was not statistically significant (p-value=0.615). Conclusion: Intrathecal dexmedetomidine added to 0.75% hyperbaric ropivacaine produced faster sensory and motor onset and prolonged block duration compared with clonidine in patients with previous scorpion bite. Both regimens were haemodynamically acceptable, but dexmedetomidine showed superior overall block characteristics and reliability
2026-08-08 | Comprehensive Ayurvedic Management of a Post-Scorpion Envenomation Ulcer: A Case Report
Scorpion envenomation is a common medical emergency in rural regions and may present with manifestations ranging from localized pain to systemic complications. Delayed presentation, inadequate wound care, or poor adherence to treatment may contribute to secondary infection, delayed healing, and post-envenomation ulcer formation. This case report describes the successful management of a post-scorpion envenomation ulcer in a 62-year-old male who presented with pain, swelling, and purulent discharge over the right great toe one week after a scorpion sting. The patient initially relied on home remedies and sought medical attention two days after the sting. Inconsistent adherence to prescribed treatment, dietary recommendations (Pathya-Apathya), and follow-up was associated with progression of the local lesion. Based on Ayurvedic clinical assessment, the condition was interpreted as Vishaja Vrana. The patient was subsequently managed with an individualized Ayurvedic treatment regimen comprising internal medications, local wound care, and dietary and lifestyle modifications in accordance with the principles of Visha Chikitsa and Vrana Chikitsa. Progressive reduction in pain, local inflammation, and purulent discharge, along with satisfactory wound healing, was observed during follow-up, culminating in complete ulcer healing. According to Ayurvedic principles, the prescribed interventions are traditionally indicated for the management of Visha-related disorders and wound healing. However, as this is a single case report, a direct therapeutic effect or venom-neutralizing activity cannot be established. Further well-designed clinical studies are warranted to evaluate the safety and efficacy of these Ayurvedic interventions in the management of post-scorpion envenomation ulcers.
2026-07-01 | Management Of Scorpion Bite Through Ayurveda: A Case Report
Agadatantra, the branch of toxicology in Ayurveda, refers to various methods of eliminating toxins from the body that arises from animate, inanimate, and artificial poisons. Scorpion stings are a serious health concern in rural areas. In Agadatantra, the symptoms of scorpion sting are explained under Vrischika visha (~scorpion venom poisoning). The main characteristics of scorpion venom poisoning are Vahnivat dahanam (~burning sensation like fire), Kshipram urdhvarohanam (~quick spreading in an upward direction), Danshe ruja tishthati (~pain remains at bite site), Sadyah ati ruk (~instant severe pain), Danshashyavata (~brownish discoloration of bite site), and Dansha toda (~ pricking type of pain at bite site). This is a case report of a 34- year- old male, who had an episode of Vrischika damsha (~scorpion bite) and presented to the outpatient department with complaints of severe edema, pain and redness, and itching. The first line of management for scorpion stings is typically symptomatic including strong analgesics, which can be systemic (opiates or paracetamol) or localized (such as a cold compress). In Ayurveda classics, Hinguadi gulika is one of the formulations mentioned in Vrischikavisha prakarana, which has been referred to as the most potent Lepana (~anointment) for scorpion venom poisoning. In comparison to existing conventional treatment modalities, Hinguadi gulika lepana is a very simple and very cost- effective procedure. Hinguadi gulika was given in combination with Kulakadi kashaya which is widely practiced in all Visha (~poison) conditions. In the present case, Hinguadi gulika and Kulakadi kashayam have shown assuring results in the management of acute scorpion envenomation.
2026-06-30 | Long-term trends in urban scorpionism under mechanical and chemical control in a Brazilian municipality
Urban scorpionism is a persistent public health challenge in medium-sized Brazilian cities. While mechanical capture is routinely employed for surveillance, chemical control was reintroduced in November 2019 to intensify interventions in high-risk microenvironments. We conducted a longitudinal observational study using monthly aggregated data (January 2014–December 2024). Interrupted time-series analysis with segmented regression was used to evaluate temporal trends, seasonality and post-intervention changes. Mechanical capture intensity was included with 0-, 3- and 6-month lags. Robust standard errors were calculated using Newey–West corrections. Scorpion sting accidents remained present year-round, with predictable seasonal peaks despite sustained mechanical control. Lagged capture analyses showed no significant association with accident counts, indicating that captures primarily reflect operational effort. The November 2019 introduction of targeted chemical control was associated with an immediate level reduction of − 7.40 accidents (95% CI −13.73 to − 1.07; p = 0.022) and a significant negative change in slope (− 0.277 accidents/month; 95% CI −0.445 to − 0.110; p = 0.001). Comparison with the counterfactual projection showed divergence between observed and expected trajectories, corresponding to an estimated cumulative difference of 1,001 cases between November 2019 and December 2024 (30.9% reduction relative to the expected continuation of the pre-intervention trend). Integrated mechanical and focal chemical control were associated, in segmented regression analyses, with reductions in both level and slope of scorpion sting incidence after 2019, consistent with attenuation of the previously observed upward trend without evidence of abrupt disruption of seasonal dynamics. Surveillance indicators reflect sustained operational activity, while chemical interventions may contribute to targeted risk reduction within persistently affected urban settings.
2026-03-24 | Integrating Traditional Knowledge in Emergency Medicine: The Role of Heat Application in Scorpion Stings
Objective: This study aims to evaluate the effects of pre-hospital hot and cold applications on analgesic requirements and symptom severity in scorpion envenomation, with the broader goal of integrating traditional practices into modern emergency care.Methods: This retrospective descriptive study included 229 adult patients who presented to Muğla Training and Research Hospital with scorpion stings between January 1, 2021, and December 31, 2022. Patients were categorized into three groups based on pre-hospital interventions: hot application (n=46), cold application (n=100), and no intervention (n=83). Clinical stage, pain intensity (VAS), analgesic use, and demographic characteristics were compared.Results: Most patients (97.8%) were classified as stage 1 envenomation. The need for NSAIDs (19.3%) and opioids (1.5%) was significantly lower in the hot application group (p
proteins
2026-06-10 | COMPONENTS AND DIAGNOSIS OF SCORPIO NVENOM AND MEDICAL IMPORTANT
Thisreview presents both the detrimental and beneficial properties of scorpion venom toxinsand discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.
2026-02-26 | Stinging Salvation: Harnessing Scorpion Venom Peptides for Revolutionary Pain Relief
from the Buthidae family, show real promise as painkillers that skip opioids altogether. They work by hitting specific ion channels and dialing down inflammation. This review gathers information on their molecular setups: disulfide-bridged types and those without, weighing in at 3 to 10 kilodaltons (kDa). Structural features include motifs stabilized by cysteines. In pain signaling, they block voltage-gated sodium channels (NaV) such as NaV1.7 and NaV1.8; take the BmK analgesic-antitumor peptide (BmK-AGAP) for example. Additionally, scorpion venom heat-resistant peptide (SVHRP) reduces microglia activity. Tests on rodents using formalin injections, acetic acid writhing, and chronic constriction injury (CCI) setups reveal pain relief that depends on dose and stacks up to morphine. Pairings like AGAP with lidocaine decrease the effective dose by half. In terms of safety, therapeutic levels have low-toxicity with a median lethal dose (LD50) over 20 mg/kg. Issues crop up with immune responses, unintended targets, and differences in venom batches. Clinical information remains thin, so gaps persist. Engineered versions could change the game for neuropathic pain, inflammatory conditions, and cancer-related discomfort. Standardization plus Phase I studies would help move this forward.
2026-02-16 | From venom peptides to neurotherapeutics: BmK defensins and short-chain peptides as modulators of ion channels.
Scorpions, having inhabited the Earth long before the emergence of humans, represent an ancient lineage of arthropods. While often regarded with fear due to their potential to induce severe pain or fatal envenomation, scorpion venoms constitute complex cocktails of bioactive molecules known as toxins. Notably, these toxic components have been repurposed in medical research as valuable sources for therapeutic development. In traditional Chinese medicine (TCM), the venom of Buthus martensii Karsch (BmK), commonly referred to as the Chinese scorpion, has been historically employed in the treatment of various neurological disorders, including epilepsy, stroke, glioma, and pain. The principal bioactive constituents of BmK venom are polypeptides that selectively target membrane ion channels. Among these, defensins and short-chain toxins (28-40 amino acids in length) have been identified as key modulators of potassium channels, TRP channels, and chloride channels. These short-chain peptides exhibit several distinct pharmacological advantages, including efficient tissue penetration due to their low molecular mass, remarkable target specificity for particular ion channel isoforms or states, inherently low immunogenicity, and considerable structural versatility that facilitates engineering (e.g., fusion strategies, point mutations) to optimize pharmacokinetics and pharmacodynamics. As such, they represent promising molecular scaffolds for drug design aimed at addressing unmet clinical needs in neurology. We summarize the most advanced drug candidates derived from BmK defensins and short-chain toxins, which exhibit activity against Kv1.3, BK, TRPV1, and other channels implicated in epilepsy, neuroinflammation, glioma, and pain. Structural and functional insights into these peptides reveal mechanisms underlying their target specificity and pharmacological advantages, such as blood-brain barrier penetration and low immunogenicity. This review underscores the originality of BmK peptides as molecular tools and lead compounds for next-generation neurology therapeutics, providing a focused resource for researchers in ion channel pharmacology and peptide-based drug design.
2026-01-18 | The Rami Five-Checkpoint Framework for AI-Guided mRNA-Encoded Neutralizers: A Unified Computational Platform for Snake and Scorpion Venom Antidote Design
Envenomation from venomous snakes and scorpions remains a major global health challenge, disproportionately affecting populations in low-resource settings where access to conventional antivenoms is limited by cost, cold-chain requirements, and species specificity. This work introduces the Rami Five-Checkpoint Framework, a unified computational methodology for the design of mRNA-encoded neutralizing proteins targeting venom toxins. The framework integrates five sequential design checkpoints: (1) toxin target selection and lethality scoring, (2) human codon optimization of mRNA sequences, (3) RNA secondary structure validation, (4) immunogenicity and toxin-binding prediction, and (5) economic feasibility assessment. The approach is demonstrated through parallel in silico case studies targeting two mechanistically distinct toxins: beta-taipoxin from the Inland Taipan (Oxyuranus microlepidotus) and the CsEv5 alpha-toxin from the Arizona bark scorpion (Centruroides sculpturatus). AI-guided de novo neutralizer designs exhibited predicted nanomolar binding affinities, high thermostability, favorable mRNA expression characteristics, and broad HLA population coverage. Cost modeling suggests the potential for substantial reductions in production cost relative to traditional animal-derived antivenoms. This study is exclusively computational and does not include experimental protocols, toxin synthesis, or clinical procedures. The framework is intended as a reusable design-time platform to accelerate antivenom research, support future experimental validation, and advance next-generation therapeutic strategies for envenomation preparedness.
2025-12-13 | Enzymatic characterization and proteomic profiling of venoms from the medically important Androctonus species.
Egyptian scorpions of the Androctonus genus (family Buthidae) produce life-threatening stings owing to their neurotoxic venom. However, the composition and enzymatic activities of their venoms remain poorly understood: We used electrophoresis to analyze the protein components of venoms collected from three Androctonus species: Androctonus amoreuxi, Androctonus australis, and Androctonus bicolor. Mass spectrometric analysis was performed to characterize the peptides present in these venoms. The phospholipase A2 (PLA2), hyaluronidase, and protease activities of the venoms were examined to gauge their potential contribution to venom toxicity. Finally, the antibacterial and hemolytic activities of the venoms were evaluated. The electrophoretic profiles of the three venoms showed features specific to each species, with distinct protein bands observed at 75, 74, 67, 48, 46, 40, and 28 kDa, along with a notable band above the 15-kDa mark. Liquid chromatography/mass spectrometry analyses were used to detect the presence of 369, 324, and 351 components in with molecular masses in the range of 500-10,000 Da in the venoms of A. amoreuxi, A. australis, and A. bicolor, respectively. Disulfide-rich peptides (three disulfide bridges) were abundant, but peptides without disulfide bonds were also detected in all venom samples. All three venoms exhibited hyaluronidase activities, whereas protease and PLA2 activities were either weak (at 1 µg and 10 µg) or undetectable, even at higher concentrations (up to 20 µg). All assays were performed using venoms standardized by dry weight to ensure consistent protein quantities. Crude venoms of A. amoreuxi and A. australis showed antibacterial activity against E. coli and B. subtilis (5-10 μg), whereas A. bicolor required 10 μg. Hydrophobic fractions (40-55 min) of A. australis alone retained this activity. This work furthers our knowledge of the enzymatic and peptide composition of Androctonus venoms, unveiling their potential in drug delivery enhancement and other biomedical applications. These findings will inform the development of better strategies for the treatment and prevention of scorpion envenomation.
vaccines
2024-09-30 | 21st century Latin American synthetic peptides for their application in antivenom production
Envenomation caused by snakes, scorpions, and spiders represents a serious public health problem in Latin America. The antivenoms used for its treatment are produced by immunizing horses repeatedly with sublethal doses of animal venoms along with the adjuvant. However, venom availability is a bottleneck. Furthermore, toxin-neutralizing antibodies are only a few of the total produced with this classical method. Therefore, high doses of antivenom are required to achieve the neutralization power, which usually causes adverse reactions in the patient. With the aim of obtaining a higher proportion of toxin-neutralizing antibodies while reducing the dependency on venom availability, alternative immunization protocols have been explored using synthetic peptides with epitopes from clinically relevant toxins. The process to design an immunogenic peptide entitles: (a) choice of the medical relevant toxins in the venom; (b) identification of the epitopes in the selected toxins; (c) improvement of peptide immunogenicity; (d) immunogen synthesis; and e) in vitro and in vivo evaluation. The present article aims to review the advances in the design of immunogenic synthetic peptides for their application in antivenom production in Latin America during the 21st century. Epitopes have been identified from many clinically important toxins in Latin American snakes (snake venom metalloproteinases, snake venom serine proteases, crotamine, phospholipases A2, and three-finger toxins), scorpions (beta-mammal/insect toxin Ts1, alpha-mammal toxin Ts2, alpha-mammal toxin Ts3, toxin Ts4, and beta-mammal Tt1g neurotoxin), and spiders (dermonecrotic toxin and delta-ctenitoxin-Pn2a). Nevertheless, their application is still experimental, even though they are ideal for large-scale and low-cost antivenom production, factors that are necessary to meet national and regional demands.
2024-05-25 | Evaluation of the immunoprotective power of a multiple antigenic peptide against Aah II toxin of Androctonus australis hector scorpion
Scorpion envenoming (SE) is a public health problem in developing countries. In Algeria, the population exposed to the risk of SE was estimated at 86.45% in 2019. Thus, the development of a vaccine to protect the exposed population against scorpion toxins would be a major advance in the fight against this disease. This work aimed to evaluate the immunoprotective effect of a Multiple Antigenic Peptide against the Aah II toxin of Androctonus australis hector scorpion, the most dangerous scorpion species in Algeria. The immunogen MAP1Aah2 was designed and tested accordingly. This molecule contains a B epitope, derived from Aah II toxin, linked by a spacer to a universal T epitope, derived from the tetanus toxin. The results showed that MAP1Aah2 was non-toxic despite the fact that its sequence was derived from Aah II toxin. The immunoenzymatic assay revealed that the 3 immunization regimens tested generated specific anti-MAP1Aah2 antibodies and cross-reacted with the toxin. Mice immunized with this immunogen were partially protected against mortality caused by challenge doses of 2 and 3 LD50 of the toxin. The survival rate and developed symptoms varied depending on the adjuvant and the challenge dose used. In the in vitro neutralization test, the immune sera of mice having received the immunogen with incomplete Freund's adjuvant neutralized a challenge dose of 2 LD50. Hence, the concept of using peptide dendrimers, based on linear epitopes of scorpion toxins, as immunogens against the parent toxin was established. However, the protective properties of the tested immunogen require further optimizations.
2022-01-24 | Long-term antibody response and protective effect induced by attenuated scorpion toxins: Involvement of memory plasma cells.
In Algeria, Androctonus australis hector scorpion envenomation remains a major problem of public health because of non-efficient therapy. The development of safe vaccine against scorpion venom could be one key strategy for the envenomation prevention. The irradiation of venom by γ-rays develops suitable immunogens which produced effective antivenom and safe vaccine. In this study, we investigated the ability of the irradiated toxic fraction (γ-FtoxG50) to induce long-term memory humoral response in immunized animals (mice and rabbits), by involving the long-lived plasma cells to prevent efficiently the lethality of scorpion envenomation. For this purpose, an appropriate immunization schedule was established in mice and rabbits using three (3) similar doses of γ-FtoxG50 associated with Alum adjuvant. Obtained results indicate that the long-term immunogenicity of γ-FtoxG50 is able to induce the long-term memory humoral response with a high level of specific antibodies. The long-term persistence of antibody levels could depend on bone marrow memory plasma cells. These cells produce continuously antibodies without antigen stimulus. Furthermore, an enhanced memory response was obtained post-repeated envenomation with toxic native venom that leads to improved protection of animals. Together, pre-existing protective antibodies and the activation of memory B-cells could induce a rapid neutralization of scorpion toxins and long-term protection against scorpion envenomation.
2022-01-20 | Strategies for Heterologous Expression, Synthesis, and Purification of Animal Venom Toxins
Animal venoms are complex mixtures containing peptides and proteins known as toxins, which are responsible for the deleterious effect of envenomations. Across the animal Kingdom, toxin diversity is enormous, and the ability to understand the biochemical mechanisms governing toxicity is not only relevant for the development of better envenomation therapies, but also for exploiting toxin bioactivities for therapeutic or biotechnological purposes. Most of toxinology research has relied on obtaining the toxins from crude venoms; however, some toxins are difficult to obtain because the venomous animal is endangered, does not thrive in captivity, produces only a small amount of venom, is difficult to milk, or only produces low amounts of the toxin of interest. Heterologous expression of toxins enables the production of sufficient amounts to unlock the biotechnological potential of these bioactive proteins. Moreover, heterologous expression ensures homogeneity, avoids cross-contamination with other venom components, and circumvents the use of crude venom. Heterologous expression is also not only restricted to natural toxins, but allows for the design of toxins with special properties or can take advantage of the increasing amount of transcriptomics and genomics data, enabling the expression of dormant toxin genes. The main challenge when producing toxins is obtaining properly folded proteins with a correct disulfide pattern that ensures the activity of the toxin of interest. This review presents the strategies that can be used to express toxins in bacteria, yeast, insect cells, or mammalian cells, as well as synthetic approaches that do not involve cells, such as cell-free biosynthesis and peptide synthesis. This is accompanied by an overview of the main advantages and drawbacks of these different systems for producing toxins, as well as a discussion of the biosafety considerations that need to be made when working with highly bioactive proteins.
2018-04-23 | Safety and efficiency of active immunization with detoxified antigen against scorpion venom: side effect evaluation.
The efficiency and safety of vaccine are the most important properties, however, as any medication, it can induce side effects. This prophylactic therapy could be used to prevent the lethal and pathophysiological effects induced after scorpion envenomation. In this study, detoxified venom associated to alum adjuvant (V*alum) is used as a vaccine against scorpion venom for immunization of mice. We evaluate the safety and the inflammatory response of this vaccine. We also investigated the protective effect of this formulation against the toxicity of native Androctonus australis hector venom. Results showed no adverse events occurred after immunization of animals. This active immunization of animals did not cause change in vascular permeability, no edema formation in the studied organs. Furthermore, there are no IgE production in sera, nor change in the morphology of the mast cells in skin tissues. However, low inflammatory response triggered by activating the recruitment of eosinophils associated to IL-4 and IL-5 release was observed. All immunized animals are protected from the toxic effects of native venom until 6 LD50 and to 7 LD50 after the second challenge. This safe vaccine preparation seems to induce a long-term protection without any risk of deleterious inflammatory response.
antibodies
2026-09-23 | Histomorphometric changes in the bronchi and lung parenchyma of rats one day after administration of venom from the scorpion Leiurus macroctenus
The lungs are one of the target organs affected by scorpion venom. Given the expansion of scorpion distribution ranges and climate change, the likelihood of venomous scorpions appearing in new territories inhabited by humans is increasing. Thus, there is a need for an in-depth morphological study of the delayed outcomes of envenomation by medically significant scorpion species. The aim of the study was to determine histological and micromorphometric changes in the bronchi and lung parenchyma of rats 1 day after administration of Leiurus macroctenus scorpion venom. The experiment involved 10 male Wistar laboratory rats maintained under vivarium conditions and divided into 2 groups: group 1 – control rats (n=5), which received physiological saline, and group 2 – rats which received scorpion venom at a dose of 28,8 μg/ml (n=5). One day after administration of Leiurus macroctenus scorpion venom, the rats were euthanized, lung samples were removed and subsequently fixed in 10 % neutral formalin or 2.5 % glutaraldehyde and 1 % osmium tetroxide, followed by standard embedding in paraffin or an epoxy resin mixture. For histological and morphometric examination of the lungs, sections with a thickness of 4-5 μm were prepared according to a standard method, followed by staining with hematoxylin-eosin and by the Azan Trichrome, as well as semithin sections with a thickness of 1-2 μm followed by methylene blue staining. Microscopy of the obtained specimens was performed using an OLIMPUS BX 41 at magnifications from ×40 to ×1000. Morphometric analysis (alveolar width, alveolar entrance width and alveolar depth, interalveolar septum thickness, and width of the conducting portion of the bronchiole) was performed using the software Quickphoto Micro 2.3. Statistical analysis was performed using the licensed software package “Statistica 6.0” using nonparametric evaluation methods. One day after administration of Leiurus macroctenus scorpion venom, pronounced degenerative-destructive changes were found in the lungs of rats, manifested by areas of interalveolar septal destruction, formation of areas of increased air content, hemorrhages, areas of dys- and atelectasis, foci of interstitial and intra-alveolar edema, and destruction of alveolocytes with the formation of cavities in which tissue detritus accumulated. Against this background, most sections showed an inflammatory reaction with marked interstitial, peribronchial and peribronchiolar infiltration by white blood cells. The bronchioles showed epithelial desquamation, thickening of the muscular layer and narrowing of the lumen, enlargement of the mucous glands and accumulation of mucus in them. Statistical analysis of morphometric parameters showed a significant decrease in alveolar width by 36.84 % (p=0.0032), alveolar entrance width by 40.52 % (p=0.0003), alveolar depth by 23.02 % (p=0.0140), and the width of the conducting portion of the respiratory bronchiole by 22.26 % (p=0.0003) compared with the control group. At the same time, the mean interalveolar septum thickness increased by 20.20 % (p=0.0065). The ratio of alveolar entrance width to alveolar depth and the ratio of the width of the conducting portion of the respiratory bronchiole to alveolar depth did not differ significantly from the control group values. Thus, Leiurus macroctenus venom causes pronounced acute complex lung injury after 1 day, manifested by a combination of alveolar destruction, edematous, hemodynamic and inflammatory changes, and impaired bronchial patency.
2026-07-20 | Scorpion envenomation in pregnancy: clinical symptoms, maternal and fetal outcomes and management strategies.
Scorpion stings pose a significant public health threat, particularly in developing regions, leading to considerable morbidity and mortality. This systematic review assesses the clinical manifestations, maternal and fetal outcomes, and evaluates the treatment approaches in pregnant women affected by scorpion stings. A systematic search was conducted in multiple databases (Web of Science, PubMed, Scopus, SID, and Magiran) from inception to October 26, 2024. Case reports, case series, and observational studies with accessible full texts were included based on predefined eligibility criteria. Data extraction included study characteristics, maternal and gestational age, scorpion species, symptoms, and pregnancy outcomes. The methodological quality of included studies was assessed independently by two reviewers using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and NIH (National Institutes of Health) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Disagreements were resolved by consensus or consultation with a third reviewer. A total of 14 studies were included in the review, comprising case reports and case series from various countries. The average maternal age was 27.14 years, and gestational age averaged 23.94 weeks. Common symptoms reported included localized pain (71.4%), nausea (14.3%), vomiting (14.3%), fever (14.3%), and abnormal vital signs (7.1%) in severe cases. The majority of studies (78.6%) indicated low symptom severity. Maternal and fetal outcomes were generally favorable, although severe outcomes, such as maternal death and intrauterine fetal death, were reported in a few cases. Antivenom was administered in only four cases (28.6%) indicating a potential gap in its use. Scorpion envenomation during pregnancy typically presents with localized pain, while severe systemic symptoms are less common. Although most maternal and fetal outcomes are favorable, serious complications such as maternal or intrauterine fetal death can occur. These findings suggest that antivenom may be underutilized in pregnant women. Therefore, we recommend: (1) increased vigilance for severe symptoms, especially abnormal vital signs; (2) timely antivenom administration in moderate-to-severe cases; and (3) standardized reporting of pregnancy-specific outcomes. Large prospective studies are urgently needed to establish evidence-based management guidelines.
2026-06-24 | Scorpionism in the Amazon: Evidence, Challenges and Actions for Controlling a Neglected Disease.
Scorpion sting envenomations impose an increasing burden in the Amazon and result in a considerable impact on public health. The genus Tityus accounts for nearly all clinically relevant cases, with T. metuendus, T. silvestris and T. obscurus being responsible for most of envenomations in the region. In the state of Amazonas, Manaus and Apuí account for most of cases reported, with an evident expansion to other regions, including the Solimões River region and the Upper Negro River region, where most of the exposed population is found in Indigenous and riverine communities. The increasing burden and high severity rates of scorpion stings in the Amazon may result from the capacity of adaptation of the endemic species to the environmental changes and limitations in providing adequate healthcare to patients. The clinical profile of patients stung by different species has similar local and systemic manifestations. In Manaus, T. metuendus is the species that is most commonly responsible for severe cases observed in children, due to them presenting circulatory collapse and acute respiratory distress, while T. apiacas and T. silvestris present systemic neurological manifestations, characterized by generalized muscle spasms described as the sensation of receiving an electric shock, apparently not reversed by the available antivenom. Scorpionism in the Amazon combines the biological complexity and variability of Tityus species and their venoms, social and environmental determinants and healthcare challenges. These features require solutions of interinstitutional, interdisciplinary networks that are capable of integrating biology, venomics, clinical medicine, public health, environmental sciences and the social sciences.
2026-04-04 | Pediatric scorpion envenomation in Tunisia: epidemiology, clinical features, therapeutic management and outcomes in a 14-year cohort study
Background Scorpion envenomation is a persistent public health concern in Tunisia, particularly in rural areas. Children are especially vulnerable due to low body weight and immature physiological systems. Methods We conducted a retrospective cohort study over a 14-year period (2011–2024) in the Pediatric Intensive Care Unit of Hedi Chaker University Hospital, Sfax, Tunisia. Children aged 0–14 years with confirmed scorpion envenomation were included. Epidemiological, clinical, biological, and outcome data were analyzed. Results Sixty-nine children were included, with a mean age of 4.6 years; two-thirds were under five years of age. Most cases occurred during summer and originated from rural areas. Systemic manifestations were present in 85.5% of patients. Moderate and severe envenomation were predominant, with 49.3% classified as Grade II and 39.1% as Grade III. Cardiac involvement was frequent, with elevated cardiac troponin observed in nearly half of cases and left ventricular dysfunction in more than one-third. Antivenom was administered in 88.4% of patients, and inotropic support was required in 25.9%. There were no fatalities; however, 18.5% of patients developed sequelae, mainly cardiac. Younger age, severe clinical presentation, seizures, respiratory distress, hyperglycemia, ventricular dysfunction, pulmonary edema, and delayed medical care (>2 hours) were significantly associated with adverse outcomes. Conclusion Pediatric scorpion envenomation often leads to systemic and cardiac complications. Early recognition and rapid management are critical to reducing morbidity.
2026-04-02 | Indian lone commercial antivenom against Indian red scorpion venom demonstrates limited immunorecognition and partial neutralisation of enzymatic, pharmacological, and some toxic effects of Heterometrus bengalensis (Indian black scorpion) venom proteins in vitro and in vivo.
Scorpion envenomation remains a significant yet under-addressed public health issue in India. Heterometrus bengalensis (HB), a medically important scorpion, can induce clinically relevant local and systemic toxicity. However, limited research has evaluated the immunological recognition and neutralisation efficacy of existing commercial anti-scorpion antivenoms (ASV) against HB venom (HBV). This study evaluated the immunological cross-reactivity and neutralisation potential of a commercial ASV against HBV using in vitro and in vivo approaches. Immunochemical assays (enzyme-linked immunosorbent assay and Western blotting) demonstrated partial immunoreactivity toward HBV proteins in the range of ~75-37 kDa, but exhibited poor recognition of low-molecular-mass proteins (<20 kDa). ASV showed feeble neutralisation of HBV enzymatic activities, HBV toxicity, and reactive oxygen species (ROS) production in Caenorhabditis elegans. ASV also showed poor protective efficacy against HBV-induced local and systemic toxicity in Swiss albino mice. ASV also failed to attenuate the HBV-induced production of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in mice. Therefore, this study highlights insufficient immunological coverage and underscores the need for species-specific antivenoms. The findings provide crucial insights for enhancing therapeutic interventions for scorpion envenomation in India.
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Drug Discovery Landscape
1 orphan drug designation for Scorpion envenomation, including 1 approved therapy.
1 orphan drug designation for Scorpion envenomation, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Centruroides immune F(ab)2 [Anascorp] | antibodies | FDA | Approved | Rare Disease Therapeutics, Inc. |
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