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A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Animal Venoms".

Deadline for manuscript submissions: closed (15 May 2026) | Viewed by 16969

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Prof. Dr. Euikyung Kim

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Department of Pharmacology and Toxicology, College of Veterinary Medicine, Gyeongsang National University, 501 Jinju Daero, Jinju 52828, Republic of Korea
Interests: venoms; toxins; molecular function; mechanism of action; drug discovery; therapeutics; signal transduction
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Special Issue Information

Dear Colleagues,

Venoms (or zootoxins) are complex mixtures of biologically active substances (proteins, peptides, enzymes, and small molecules) produced by animals, such as snakes, spiders, scorpions, and some marine organisms. These substances are typically delivered through specialized anatomical structures like fangs, stingers, or spines.

This Special Issue, “Venoms and Drugs”, aims to explore the fascinating interface between venom-derived compounds and their potential therapeutic applications. Venoms, often viewed primarily as harmful substances, harbor a myriad of bioactive molecules with unique pharmacological properties. These molecules have shown promise in the development of novel drugs for a variety of diseases, from chronic pain and cancer to cardiovascular and infectious diseases.

We encourage the submission of original research articles, reviews, and case studies that delve into the biological, chemical, and pharmacological aspects of venoms. Contributions that provide insights into the molecular mechanisms of venom action, innovative drug design, and clinical applications are particularly welcome.

Potential topics for this Special Issue include, but are not limited to, the following:

Isolation and characterization of venom components;
Molecular mechanisms of venom action;
Venom-derived peptides and proteins as therapeutic agents;
Drug development from venom components;
Preclinical and clinical studies on venom-based drugs;
Venom toxins and their receptors;
Synthetic and bioengineered toxin analogs;
Venoms in pain management and neuroprotection.

We look forward to receiving valuable contributions that will help advance our understanding of the therapeutic potential of venoms and foster the development of innovative treatments.

Prof. Dr. Euikyung Kim
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

venom components
molecular mechanism
preclinical
clinical
toxin receptors
toxin analogs

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Published Papers (10 papers)

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19 pages, 1202 KB

Open AccessArticle

Antimicrobial Activity of Micrurus Venoms and Bioactive Films Functionalized with Purified L-Amino Acid Oxidase

by Vitelbina Núñez Rangel, Paola Rey-Suárez, Daniel Buitrago-Chinchilla, Laura Reyes-Méndez, Leidy Gómez-Sampedro, Alejandro Carmona-Jiménez, Mateo Rivillas-Ochoa and Adriana Muñoz-Bravo

Toxins 2026, 18(6), 240; https://doi.org/10.3390/toxins18060240 - 22 May 2026

Abstract

Phytopathogenic bacteria and fungi significantly reduce fruit and vegetable yields, resulting in substantial economic losses. Conventional management relies on synthetic agrochemicals; however, their intensive use poses risks to human health, environmental integrity, and biodiversity. Snake venoms have evolved under selective pressure, developing specialized components with potent antimicrobial properties as part of a defense mechanism against prey-borne microorganisms. This study evaluated the inhibitory potential of Micrurus venoms against pathogens of agricultural interest and developed bioactive gelatin-based films incorporated with purified L-amino acid oxidases (LAAOs) as a novel biocontrol strategy. Venoms from M. ancoralis, M. mipartitus, and M. dumerilii exhibited significant growth inhibition against Xanthomonas and Fusarium strains. The primary active component was identified as LAAO through biological activity and mass spectrometry. Biofilms were formulated by incorporating M. ancoralis venom and its purified LAAO into a gelatin matrix. Physicochemical and microbiological characterization, alongside in situ assays on strawberries, demonstrated that the functionalized biofilms retained potent antimicrobial activity. Furthermore, LAAO incorporation did not significantly alter the physicochemical properties of the fruit but effectively extended shelf life by reducing weight loss and maintaining sensory appearance. These findings highlight the biotechnological potential of elapid venom components in the development of alternatives for phytopathogen control and active food packaging. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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12 pages, 918 KB

Open AccessArticle

Five-Year Real-World Outcomes of Hymenoptera Venom Immunotherapy: Clinical Effectiveness and Immunological Modifications

by Claudia Panzera, Sebastiano Gangemi and Luisa Ricciardi

Toxins 2026, 18(4), 187; https://doi.org/10.3390/toxins18040187 - 15 Apr 2026

Viewed by 588

Abstract

Hymenoptera venom allergy is a cause of anaphylaxis, which significantly affects patients’ daily lives due to the constant fear of accidental stings. Venom immunotherapy (VIT) is the only treatment capable of preventing severe systemic reactions (SSRs). Limited long-term real-life data are available, integrating both clinical and immunological outcomes. A five-year prospective observational study was conducted on 35 patients with a history of SSR who underwent VIT at a tertiary allergy center in Southern Italy; two of them had a diagnosis of systemic mastocytosis. Most patients were sensitized to Vespula, but others to Apis, Polistes dominula and Vespa crabro, reflecting the exposure pattern characteristic of Mediterranean regions. Clinical outcomes following accidental re-stings and serological trends, including total IgE, venom-specific IgE, and baseline serum tryptase, were assessed at treatment initiation and after five years of maintenance therapy. During the entire follow-up, all patients tolerated VIT. No SSRs occurred after accidental stings in 17/35 patients, confirming clinical protection achieved with VIT. Vespula serum-specific IgE presented a highly significant decrease; total IgE, tryptase and specific IgE for Apis, Polistes dominula and Vespa crabro showed a statistically significant decrease. Our findings reinforce the role of VIT as a well-tolerated, effective and disease-modifying treatment in a real-world setting. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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15 pages, 1434 KB

Open AccessArticle

New Insights into the Bioenergetic and Immunomodulatory Properties of Phospholipases A₂ from Bothrops diporus Venom

by Daniela J. Sasovsky, Ana K. Oliveira, Dilza Trevisan Silva, Gonzalo A. Ojeda, Cristopher Almarza, Bruno Lomonte, Jay W. Fox, Félix A. Urra and Soledad Bustillo

Toxins 2026, 18(2), 114; https://doi.org/10.3390/toxins18020114 - 23 Feb 2026

Viewed by 997

Abstract

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

(This article belongs to the Special Issue Venoms and Drugs)

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21 pages, 3236 KB

Open AccessArticle

Establishing the Kenya National Antivenom Quality Control Laboratory: Preclinical Efficacy Results of Four Antivenoms Against Venoms from the “Big Five” Snake Species in Kenya

by Valentine Musabyimana, John M. Kagira, Jacob Lubuya, Caroline W. Ngugi, Brian M. Musau, Wathuto Ogopotse, Geoffrey Maranga, Dennis Kotti, Pamela M. Khasandi, Ezekiel Adino, Brent C. Thomas, Cassandra M. Modahl, Peter G. Mwethera, Robert A. Harrison, Nicholas R. Casewell and George O. Oluoch

Toxins 2026, 18(2), 106; https://doi.org/10.3390/toxins18020106 - 19 Feb 2026

Cited by 1 | Viewed by 1727

Abstract

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

(This article belongs to the Special Issue Venoms and Drugs)

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23 pages, 4900 KB

Open AccessArticle

Biodiversity-Driven Screening of Amphibian Skin Secretions for Inflammatory Modulation in Joint Diseases

by Douglas Souza Oliveira, César Alexandre, Miryam Paola Alvarez-Flores, Isadora Maria Villas-Boas, Hugo Vigerelli, Isabel de Fátima Correia Batista, Michelle Cristiane Bufalo, Nancy Starobinas, Flávio Lichtenstein, Rafael Marques-Porto, Marcus Buri, Viviane Portas-Lopes, Pedro Luiz Mailho-Fontana, Marta Maria Antoniazzi, Denise Vilarinho Tambourgi, Ana Marisa Chudzinski-Tavassi, Catarina Teixeira, Carlos Jared and Olga Martinez Ibañez

Toxins 2025, 17(9), 464; https://doi.org/10.3390/toxins17090464 - 17 Sep 2025

Cited by 1 | Viewed by 1455

Abstract

This study explores the direct effects of amphibian skin secretions on human cells involved in joint diseases, aiming to identify species with potential for inflammatory modulation. Secretions were obtained from sixteen species distributed across Brazilian biomes and one European species. Following biochemical characterization, human chondrocytes, synoviocytes, and macrophages were treated with secretions for 24 h. The cytotoxicity and modulation of the IL-6, IL-8, TNF-α, and IL-1β release were assessed. Synoviocytes showed the greatest resistance to cytotoxic effects, though sensitivity varied by species. Secretions from Trachycephalus mesophaeus, Pipa carvalhoi, and Phyllomedusa bahiana exhibited the highest cytotoxicity. At non-cytotoxic concentrations, P. carvalhoi and Leptodactylus fuscus strongly induced IL-6 and IL-8 in chondrocytes and synoviocytes, with P. carvalhoi also stimulating IL-1β and TNF-α release in macrophages. Among Bufonidae species, particularly Rhinella jimi and Bufo bufo, were potent inducers of TNF-α and IL-1β in macrophages. Secretions lacking pro-inflammatory effects were further tested for anti-inflammatory activity. P. bahiana reduced TNF-α production in stimulated macrophages and IL-6 in synoviocytes, while Siphonops annulatus and T. mesophaeus reduced LPS-induced TNF-α in macrophages. Our data underscore the rich biodiversity of amphibians, supporting the bioprospecting of their cutaneous secretions. These data reveal substantial potential for uncovering bioactive compounds with pharmacological applications. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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12 pages, 2497 KB

Open AccessArticle

Atomistic-Level Structural Insight into Vespa Venom (Ves a 1) and Lipid Membrane Through the View of Molecular Dynamics Simulation

by Nawanwat Chainuwong Pattaranggoon, Withan Teajaroen, Sakda Daduang, Supot Hannongbua, Thanyada Rungrotmongkol and Varomyalin Tipmanee

Toxins 2025, 17(8), 387; https://doi.org/10.3390/toxins17080387 - 31 Jul 2025

Viewed by 1430

Abstract

This study used all-atom molecular dynamics simulations to investigate the structural dynamics of Ves a 1, a phospholipase from Vespa affinis venom, and its interactions within a lipid membrane environment, both alone and in the presence of the inhibitor voxilaprevir. Simulations conducted over [...] Read more.

µ

s for triplicate runs demonstrated system stability and convergence of structural properties. Our findings reveal that Ves a 1 engages in dynamic interactions with the lipid bilayer, involving key regions such as its lids, catalytic triad, and auxiliary site. The presence of voxilaprevir was observed to subtly alter these membrane interaction patterns and influence the enzyme’s catalytic area, reflecting the inhibitor’s impact within its physiological context. These results emphasize the crucial role of the lipid bilayer in shaping enzyme function and highlight voxilaprevir as a promising candidate for further inhibitor development, offering vital insights for rational drug design targeting membrane-associated proteins. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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17 pages, 1736 KB

Open AccessEditor’s ChoiceArticle

Electrical Cell Impedance Sensing (ECIS): Feasibility of a Novel In Vitro Approach to Studying Venom Toxicity and Potential Therapeutics

by Abhinandan Choudhury, Kaitlin Linne, Tommaso C. Bulfone, Tanvir Hossain, Abu Ali Ibn Sina, Philip L. Bickler, Bryan G. Fry and Matthew R. Lewin

Toxins 2025, 17(4), 193; https://doi.org/10.3390/toxins17040193 - 11 Apr 2025

Cited by 2 | Viewed by 3048

Abstract

Snakebite envenoming is often discussed in terms of lethality and limb loss, but local tissue injury and coagulotoxic effects of venom are significantly more common acute manifestations of snakebite envenoming (SBE). Local tissue injury and the hemorrhagic and coagulotoxic effects of venom are challenging to study in live animals and can be ethically fraught due to animal welfare concerns such that attention to the 3Rs of animal welfare motivates the development of in vitro techniques in this arena. Herein, we tested the use of a wound-healing study technique known as Electric Cell-Substrate Impedance Sensing (ECIS) to assess populations of cultured cells exposed to venom with or without sPLA₂ and/or metalloprotease inhibitors (varespladib and marimastat, respectively). For comparison, the StarMax coagulation analyzer for coagulotoxicity was further used to evaluate the venoms and the neutralizing capabilities of the abovementioned direct toxin inhibitors (DTIs) against the same venoms examined using ECIS. Three viper and three elapid venoms that were examined for their effects on H1975 cells were Agkistrodon contortrix (Eastern Copperhead), Crotalus helleri (Southern Pacific Rattlesnake), and Vipera ammodytes (Horned Viper) and Naja atra (Chinese Cobra), Naja mossambica (Mozambique Spitting Cobra), and Naja nigricollis (Black-necked Spitting Cobra), respectively. The combination of cellular and coagulation techniques appears to usefully discriminate the in vitro capabilities and limitations of specific inhibitors to inhibit specific venom effects. This study suggests that ECIS with or without concomitant coagulation testing is a feasible method to generate reproducible, meaningful preclinical data and could be used with any type of cell line. Importantly, this approach is both quantitative and has the potential of reducing animal use and suffering during the evaluation of potential therapeutics. To further evaluate the potential of this method, rescue studies should be performed. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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20 pages, 3095 KB

Open AccessArticle

The Anthelmintic Activity of Stonefish (Synanceia spp.) Ichthyocrinotoxins and Their Potential as Novel Therapeutics

by Danica Lennox-Bulow, Jamie Seymour, Alex Loukas and Michael Smout

Toxins 2025, 17(2), 66; https://doi.org/10.3390/toxins17020066 - 2 Feb 2025

Cited by 3 | Viewed by 2332

Abstract

Parasitic gastrointestinal worms (i.e., helminths) remain a significant global health and economic burden. The increasing inefficacy of current anthelmintic drugs against parasitic diseases necessitates the discovery of novel therapeutic options. This study investigated the anthelmintic properties and therapeutic potential of stonefish ichthyocrinotoxins (i.e., secreted skin toxins). xWORM (xCELLigence Worm Real-Time Motility Assay) was used to evaluate the anthelmintic activity of ichthyocrinotoxins from two stonefish species, Synanceia horrida (Estuarine Stonefish) and Synanceia verrucosa (Reef Stonefish), against the infective third-stage larvae of Nippostrongylus brasiliensis (Rodent Hookworm). Both toxins demonstrated potent anthelmintic effects, with S. horrida ichthyocrinotoxin exhibiting greater potency (IC₅₀ = 196.0 µg/mL) compared to ichthyocrinotoxin from S. verrucosa (IC₅₀ = 329.7 µg/mL). Fractionation revealed that the anthelmintic activity of S. verrucosa is likely driven by synergistic interactions between the large (>3 kDa) and small (<3 kDa) components. In contrast, the small components isolated from S. horrida ichthyocrinotoxin were responsible for the majority of the observed activity, making them a more attractive therapeutic candidate. Furthermore, despite the cytotoxicity of crude S. horrida ichthyocrinotoxin against human skin and bile duct cell lines, the isolated small components exhibited potent anthelmintic effects (IC₅₀ = 70.5 µg/mL) with negligible cytotoxicity (<10% decrease in survival at 100 µg/mL). While further research is necessary to fully characterise these compounds and assess their clinical suitability, this study highlights the potential of stonefish ichthyocrinotoxins as a novel source of anthelmintic therapeutics. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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14 pages, 2748 KB

Open AccessArticle

Identification of New Angiotensin-Converting Enzyme Inhibitory Peptides Isolated from the Hydrolysate of the Venom of Nemopilema nomurai Jellyfish

by Ramachandran Loganathan Mohan Prakash, Deva Asirvatham Ravi, Du Hyeon Hwang, Changkeun Kang and Euikyung Kim

Toxins 2024, 16(9), 410; https://doi.org/10.3390/toxins16090410 - 20 Sep 2024

Cited by 3 | Viewed by 2771

Abstract

Recently, jellyfish venom has gained attention as a promising reservoir of pharmacologically active compounds, with potential applications in new drug development. In this investigation, novel peptides, isolated from the hydrolysates of Nemopilema nomurai jellyfish venom (NnV), demonstrate potent inhibitory activities against angiotensin-converting enzyme (ACE). Proteolytic enzymes—specifically, papain and protamex—were utilized for the hydrolysis under optimized enzymatic conditions, determined by assessing the degree of hydrolysis through the ninhydrin test. Comparative analyses revealed that papain treatment exhibited a notably higher degree of NnV hydrolysis compared to protamex treatment. ACE inhibitory activity was quantified using ACE kit-WST, indicating a substantial inhibitory effect of 76.31% for the papain-digested NnV crude hydrolysate, which was validated by captopril as a positive control. The separation of the NnV-hydrolysate using DEAE sepharose weak-anion-exchange chromatography revealed nine peaks under a 0–1 M NaCl stepwise gradient, with peak no. 3 displaying the highest ACE inhibition of 96%. The further purification of peak no. 3 through ODS-C18 column reverse-phase high-performance liquid chromatography resulted in five sub-peaks (3.1, 3.2, 3.3, 3.4, and 3.5), among which 3.2 exhibited the most significant inhibitory activity of 95.74%. The subsequent analysis of the active peak (3.2) using MALDI–TOF/MS identified two peptides with distinct molecular weights of 896.48 and 1227.651. The peptide sequence determined by MS/MS analysis revealed them as IVGRPLANG and IGDEPRHQYL. The docking studies of the two ACE-inhibitory peptides for ACE molecule demonstrated a binding affinity of −51.4 ± 2.5 and −62.3 ± 3.3 using the HADDOCK scoring function. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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Review

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17 pages, 1831 KB

Open AccessReview

Snake Venom PLA₂ as Anticoagulant Agents: Role of Crotoxin, from Crotalus durissus Rattlesnake, in Hemostasis

by Lisele Maria Brasileiro-Martins, Greene Dias Marques, Jéssica Burlamaque Maciel, Márcia Neiva, Thaís Pinto Nascimento, David Jose Estrada Reyes, Alessandro Júnio Campelo Feitosa, Sofia Angiole-Cavalcante, Priscila Ferreira de Aquino, Jacqueline de Almeida Gonçalves Sachett, Wuelton Marcelo Monteiro and Marco Aurélio Sartim

Toxins 2025, 17(12), 583; https://doi.org/10.3390/toxins17120583 - 5 Dec 2025

Cited by 1 | Viewed by 1129

Abstract

Snake venoms are rich sources of bioactive molecules that modulate hemostasis and, among these, anticoagulant snake venom phospholipases A₂ (sPLA₂) are found in a range of snake venoms. Crotoxin (CTX), from the Crotalus durissus rattlesnake, is a heterodimeric PLA₂ complex, and literature has reported its mechanisms in anticoagulant activity. The present review revisits the biological roles of anticoagulant sPLA₂ and critically examines evidence on CTX in hemostatic regulation, aiming to clarify its mechanisms and therapeutic promise. CTX exerts anticoagulant activity via enzymatic hydrolysis of procoagulant phospholipids and direct interaction with coagulation factors, disrupting key complex assembly. It also counteracts inflammation-induced coagulation by modulating leukocyte- and endothelial-derived mediators, restoring balance among anticoagulant, procoagulant, and fibrinolytic pathways. Effects on platelet function appear comparatively modest, ranging from less potent pro-aggregatory activity to negligible aggregation. The dual anticoagulant and anti-inflammatory properties of CTX highlight its potential as a model for novel antithrombotic agents in hypercoagulable and inflammation-driven disorders, despite toxicological concerns that necessitate cautious pharmacological exploration. Full article

(This article belongs to the Special Issue Venoms and Drugs)

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