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Toxins
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Biochemistry, Pathology and Applications of Venoms
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Biochemistry, Pathology and Applications of Venoms

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

Deadline for manuscript submissions: 31 July 2026 | Viewed by 16913

Special Issue Editor

Prof. Dr. Sakthivel Vaiyapuri

E-Mail Website
Guest Editor
School of Pharmacy, University of Reading, Reading RG6 6UB, UK
Interests: venom research; sequence, structure and functional analysis of venom proteins; development of diagnostic and improved therapeutic strategies for snakebites; the impact of venoms on the cardiovascular system; clinical management of snakebites in patients; policy development for snakebites
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Venoms are complex biochemical mixtures produced by venomous animals such as snakes and invertebrate species, including spiders and scorpions. Venoms contain small peptides and enzymatic and non-enzymatic proteins, as well as several other organic and inorganic molecules that target specific physiological systems. Venoms mainly include neurotoxins, haemotoxins, cytotoxins, and myotoxins, which interfere with nerve signalling, blood clotting, and tissue integrity, respectively. They can cause pain, paralysis, tissue necrosis, respiratory failure, and coagulation disorders following envenoming in humans. Therefore, researching venoms is vital for developing better antivenoms and medical treatments. Beyond their toxicity, venoms have groundbreaking medical applications. For example, a cone snail venom has led to non-opioid painkillers, specific snake venom peptides have inspired blood pressure medications, and certain venom proteins are being studied for anticoagulants, stroke treatments, and cancer therapy. Additionally, venoms provide better insights into neurological diseases like epilepsy and Alzheimer’s disease. Therefore, the study of venoms bridges biochemistry, toxicology, and pharmacology and turns deadly venom toxins into therapeutic tools while improving treatments for envenoming. As venom research expands, it continues to yield life-saving drugs and new scientific breakthroughs, demonstrating the importance of understanding these powerful natural resources. Hence, I would like to invite researchers to share their novel findings on the biochemistry, pathology, and clinical applications of any venoms or their isolated toxins in this Special Issue. I look forward to receiving your articles.

Prof. Dr. Sakthivel Vaiyapuri
Guest Editor

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Keywords

  • venom
  • snakes
  • venomous invertebrates
  • venom toxins
  • clinical applications of venoms and toxins
  • biochemical composition of venoms
  • pathology of venoms
  • envenomation effects

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Published Papers (7 papers)

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Research

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22 pages, 3114 KB  
Article
Effects of Cape Cobra (Naja nivea) Venom and Its Isolated Protein on the Modulation of Platelet Activation
by Mahtab Khatibi, José R. Almeida, Ashifa Al Juwaiser, Soheil Gilabadi, Ketan Patel and Sakthivel Vaiyapuri
Toxins 2026, 18(5), 211; https://doi.org/10.3390/toxins18050211 - 30 Apr 2026
Viewed by 343
Abstract
The Cape cobra (Naja nivea), one of Africa’s most lethal snakes, can cause rapid, life-threatening paralysis. However, the impact of this venom on platelet function and blood coagulation remains poorly understood. To address this gap, we investigated the enzymatic profiles and [...] Read more.
The Cape cobra (Naja nivea), one of Africa’s most lethal snakes, can cause rapid, life-threatening paralysis. However, the impact of this venom on platelet function and blood coagulation remains poorly understood. To address this gap, we investigated the enzymatic profiles and the impacts of N. nivea venom on multiple aspects of haemostasis using human whole blood. Our results illustrate that Cape cobra venom significantly increases clotting time in rotational thromboelastometry without affecting other coagulation parameters. This venom significantly inhibits platelet aggregation and activation yet does not exert cytotoxic effects on platelets. The venom was subsequently fractionated using reverse-phase high-performance liquid chromatography, and the most potent purified fraction was identified as a cytotoxin (three-finger toxin) through mass spectrometry. This purified fraction showed an inhibitory effect on platelet activity. These findings highlight that N. nivea venom can induce haemotoxicity in addition to neurotoxicity. Moreover, three-finger toxins may be promising candidates for bioprospecting to develop novel antithrombotic agents. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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14 pages, 1385 KB  
Article
Paediatric Snakebite Toxicity up to Compartment Syndrome: A Ten-Year Retrospective Study in Iasi, Romania
by Bogdan Caba, Sidonia Petronela Susanu, Ioana Cezara Caba, Tamara Roșu-Solange, Bogdan Huzum, Vasile Eduard Roșu, Ileana Katerina Ioniuc, Maria Adriana Mocanu and Iuliana Magdalena Starcea
Toxins 2026, 18(3), 128; https://doi.org/10.3390/toxins18030128 - 2 Mar 2026
Viewed by 698
Abstract
Viper bites are medical emergencies that can develop into serious clinical complications and can endanger the life of the paediatric patient. This observational retrospective study analyses 24 cases of viper bites involving paediatric patients (<18 years) encountered over 10 years (2016–2025) in the [...] Read more.
Viper bites are medical emergencies that can develop into serious clinical complications and can endanger the life of the paediatric patient. This observational retrospective study analyses 24 cases of viper bites involving paediatric patients (<18 years) encountered over 10 years (2016–2025) in the emergency department of Saint Mary Emergency Hospital of Iasi, Romania, with a focus on those requiring specialised surgical monitoring. Sociodemographic factors, toxicity, and surgical management of snakebites were analysed. In 83.33% cases, viper bites were found on the lower limb. The retrospective study was completed through an in-depth analysis of two representative cases, with a particular focus on the evolution up to compartment syndrome. Of the 24 cases presented in the Emergency Department, one was a rare and severe case, which evolved into compartment syndrome and required fasciotomy to save the limb in the Plastic Surgical Department. Another one, with the bite localised at the upper limb, had perilesional oedema, without skin colour changes or secretions, preservation of joint contours, and normal nail colouration. Both were analysed and described in detail with all available data (images, investigations, etc.) to highlight pathophysiological and therapeutic aspects. Appropriate, multidisciplinary treatment considerably improves the functional prognosis of patients with viper bites; administration of antivenom and selective fasciotomy contribute to successful outcomes. The study emphasises that viper bites in children remain a public health problem in Romania and require prompt and multidisciplinary treatment. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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18 pages, 5407 KB  
Article
Differential Effects of Marimastat and Prinomastat on the Metalloprotease Activity of Various Snake Venoms
by Mahtab Khatibi, José R. Almeida, Soheil Gilabadi, David Ramírez, Paulina Valenzuela-Hormazábal, Ketan Patel and Sakthivel Vaiyapuri
Toxins 2025, 17(12), 571; https://doi.org/10.3390/toxins17120571 - 26 Nov 2025
Cited by 1 | Viewed by 1766
Abstract
Snakebite envenoming is a neglected tropical disease, responsible for approximately 140,000 deaths globally each year. Vipers and elapid snakes represent the most significant snake families in medical contexts, exhibiting a variety of venom components and clinical effects in bite victims. Metalloproteases, a primary [...] Read more.
Snakebite envenoming is a neglected tropical disease, responsible for approximately 140,000 deaths globally each year. Vipers and elapid snakes represent the most significant snake families in medical contexts, exhibiting a variety of venom components and clinical effects in bite victims. Metalloproteases, a primary component of venoms, are mainly accountable for haemotoxic and myotoxic effects. Although predominantly found in viper venoms, these enzymes are also present in varying levels in elapid snake venoms. Marimastat and prinomastat are matrix metalloprotease inhibitors initially developed as cancer therapies. Recently, extensive research has focused on these inhibitors to neutralise venom metalloproteases. However, their effects on different viper and elapid snake venoms remain unclear. Here, we report the sensitivity of seven elapid venoms (specifically, cobras) and 12 viper venoms to marimastat and prinomastat, utilising selective in vitro experiments and molecular docking analyses performed using representative metalloprotease (VAP2, a viper metalloprotease from the venom of Crotalus atrox and an elapid metalloprotease from the venom of Naja atra) structures. Both compounds inhibited the metalloprotease, fibrinogenolytic, and caseinolytic activities of most viper venoms. While prinomastat displayed prominent inhibitory effects on cobra venoms in these assays, marimastat demonstrated limited inhibitory effects on these venoms. These findings illustrate the role of matrix metalloprotease inhibitors in modulating metalloprotease activities across a range of viper and cobra venoms. Collectively, this study establishes the differential effects of marimastat and prinomastat on various levels of metalloproteases present in viper and elapid venoms. This will enhance understanding of the abundance of metalloproteases in snake venoms and their sensitivity to different matrix metalloprotease inhibitors. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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17 pages, 2248 KB  
Article
Expression of L-Amino Acid Oxidase (Ml-LAAO) from the Venom of the Micrurus lemniscatus Snake in a Mammalian Cell System
by Ari Junio de Oliveira Costa, Alessandra Matavel, Patricia Cota Campos, Jaqueline Leal dos Santos, Ana Caroline Zampiroli Ataide, Sophie Yvette Leclercq, Valéria Gonçalves de Alvarenga, Sergio Caldas, William Castro-Borges and Márcia Helena Borges
Toxins 2025, 17(10), 491; https://doi.org/10.3390/toxins17100491 - 2 Oct 2025
Viewed by 1445
Abstract
Animal venoms are rich in bioactive molecules with promising biotechnological potential. They comprise both protein and non-protein toxins. Among the protein toxins are enzymes, such as phospholipases A2, proteases and L-amino acid oxidases (LAAOs). LAAOs exhibit antimicrobial, antiparasitic, antiviral, and anticancer [...] Read more.
Animal venoms are rich in bioactive molecules with promising biotechnological potential. They comprise both protein and non-protein toxins. Among the protein toxins are enzymes, such as phospholipases A2, proteases and L-amino acid oxidases (LAAOs). LAAOs exhibit antimicrobial, antiparasitic, antiviral, and anticancer effects, making them potential candidates for biotechnological applications. These activities are linked to their ability to catalyze oxidative reactions that convert L-amino acids into α-keto acids, releasing ammonia and hydrogen peroxide, which contribute to the immune response, pathogen elimination, and oxidative stress. However, in snakes of the Micrurus genus, LAAOs generally represent a small portion of the venom (up to ~7%), which limits their isolation and study. To overcome this, the present study aimed to produce Ml-LAAO, the enzyme from Micrurus lemniscatus, through heterologous expression in mammalian cells. The gene sequence was inferred from its primary structure and synthesized into the pSecTag2B vector for expression in HEK293T cells. After purification using a His Trap-HP column, the presence of recombinant Ml-LAAO (Ml-LAAOrec) was confirmed by Western blot and mass spectrometry, validating its identity. These results support successful recombinant expression of Ml-LAAO and highlight its potential for scalable production and future biotechnological applications. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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20 pages, 4713 KB  
Article
X Marks the Clot: Evolutionary and Clinical Implications of Divergences in Procoagulant Australian Elapid Snake Venoms
by Holly Morecroft, Christina N. Zdenek, Abhinandan Chowdhury, Nathan Dunstan, Chris Hay and Bryan G. Fry
Toxins 2025, 17(8), 417; https://doi.org/10.3390/toxins17080417 - 18 Aug 2025
Cited by 2 | Viewed by 6901
Abstract
Australian elapid snakes possess potent procoagulant venoms, capable of inducing severe venom-induced consumption coagulopathy (VICC) in snakebite victims through rapid activation of the coagulation cascade by converting the FVII and prothrombin zymogens into their active forms. These venoms fall into two mechanistic categories: [...] Read more.
Australian elapid snakes possess potent procoagulant venoms, capable of inducing severe venom-induced consumption coagulopathy (VICC) in snakebite victims through rapid activation of the coagulation cascade by converting the FVII and prothrombin zymogens into their active forms. These venoms fall into two mechanistic categories: FXa-only venoms, which hijack host factor Va, and FXa:FVa venoms, containing a complete venom-derived prothrombinase complex. While previous studies have largely focused on human plasma, the ecological and evolutionary drivers behind prey-selective venom efficacy remain understudied. Here, thromboelastography was employed to comparatively evaluate venom coagulotoxicity across prey classes (amphibian, avian, rodent) and human plasma, using a taxonomically diverse selection of Australian snakes. The amphibian-specialist species Pseudechis porphyriacus (Red-Bellied Black Snake) exhibited significantly slower effects on rodent plasma, suggesting evolutionary refinement towards ectothermic prey. In contrast, venoms from dietary generalists retained broad efficacy across all prey types. Intriguingly, notable divergence was observed within Pseudonaja textilis (Eastern Brown Snake): Queensland populations of this species, and all other Pseudonaja (brown snake) species, formed rapid but weak clots in prey and human plasma. However, the South Australian populations of P. textilis produced strong, stable clots across prey plasmas and in human plasma. This is a trait shared with Oxyuranus species (taipans) and therefore represents an evolutionary reversion towards the prothrombinase phenotype present in the Oxyuranus and Pseudonaja last common ancestor. Clinically, this distinction has implications for the pathophysiology of human envenomation, potentially influencing clinical progression, including variations in clinical coagulopathy tests, and antivenom effectiveness. Thus, this study provides critical insight into the ecological selection pressures shaping venom function, highlights intraspecific venom variation linked to geographic and phylogenetic divergence, and underscores the importance of prey-focused research for both evolutionary toxinology and improved clinical management of snakebite. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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Review

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35 pages, 1531 KB  
Review
Exploring the Pain-Relieving Potential: Unveiling Antinociceptive Properties in Animal Venoms and Toxins
by Davi Gomes Angstmam, Bruna Cristina Jeronimo, Joeliton dos Santos Cavalcante, Ana Flávia Marques Pereira, Cristiane Flora Villarreal, Daniel Carvalho Pimenta and Rui Seabra Ferreira Junior
Toxins 2026, 18(2), 69; https://doi.org/10.3390/toxins18020069 - 27 Jan 2026
Viewed by 1387
Abstract
Currently, commercially available pain medications can cause adverse effects. Within this framework, researchers have been exploring new drug candidates derived from animal venoms and toxins. The objective of this study was to investigate the number of molecules with potential for pain relief derived [...] Read more.
Currently, commercially available pain medications can cause adverse effects. Within this framework, researchers have been exploring new drug candidates derived from animal venoms and toxins. The objective of this study was to investigate the number of molecules with potential for pain relief derived from animal venoms and toxins, which could potentially contribute to the development of new biopharmaceuticals. We conducted a literature search in January 2025, covering the period from 1960 to 2025, in two Latin American and nine international scientific databases. The results consisted of 212 articles selected for review. From these articles, 152 toxins and venoms with analgesic potential were identified and classified into 14 different types of pharmacological targets. The peptides investigated, with masses between 500 Da and 5000 Da, are strong candidates for alternative biopharmaceuticals. Most of the toxins found interact with ion channels, representing an alternative to commercially available drugs. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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25 pages, 726 KB  
Review
Anticancer Activity of Snake Venom Against Breast Cancer: A Scoping Review
by Eun-Jin Kim, Jang-Kyung Park, Soo-Hyun Sung and Hyun-Kyung Sung
Toxins 2025, 17(10), 477; https://doi.org/10.3390/toxins17100477 - 25 Sep 2025
Cited by 3 | Viewed by 3513
Abstract
Breast cancer remains a leading cause of cancer-related mortality worldwide, necessitating innovative therapeutic approaches. This scoping review summarizes experimental evidence on the anticancer activity of snake venom and its bioactive components against breast cancer, drawing from a variety of in vitro and in [...] Read more.
Breast cancer remains a leading cause of cancer-related mortality worldwide, necessitating innovative therapeutic approaches. This scoping review summarizes experimental evidence on the anticancer activity of snake venom and its bioactive components against breast cancer, drawing from a variety of in vitro and in vivo studies. Aimed at critically evaluating the therapeutic potential and underlying mechanisms, this review consolidates findings on venoms from multiple snake species, including both crude preparations and purified proteins or peptides, revealing a diversity of mechanisms of action. Reported effects include induction of apoptosis, generation of reactive oxygen species, disruption of cell membrane integrity, inhibition of cell proliferation and metastasis, and modulation of oncogenic signaling pathways. In vivo findings further indicate tumor growth inhibition and, in some cases, enhanced efficacy when venom-based agents are combined with nanoparticle delivery systems or conventional anticancer drugs. However, a significant proportion of evidence is limited to in vitro studies, with substantial heterogeneity in venom sources, extraction methods, dosages, and cancer models, which constrains generalizability. There is also a lack of systematic data on long-term toxicity, immunogenicity, off-target effects, pharmacokinetics, and formulation challenges. Taken together, these findings highlight snake venom-derived compounds as promising multi-targeted anticancer agents but underscore the urgent need for standardized formulations, rigorous preclinical safety assessments, and translational research to bridge the gap to clinical application. Future investigations should aim to isolate novel venom-derived compounds, refine delivery strategies, and undertake rigorous preclinical safety and pharmacokinetic studies—ultimately moving toward early-phase clinical evaluation to bridge the translational gap and assess the therapeutic potential of these agents. Full article
(This article belongs to the Special Issue Biochemistry, Pathology and Applications of Venoms)
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