Introduction

Venoms are complex mixtures of bioactive proteins and peptides that have evolved in various animals for capturing prey, defence, and deterring competitors1. It is estimated that venoms are produced in approximately 15% of all known animal species2. From the potent neurotoxins of snakes, to the cytotoxic molecules found in insect stings, venoms exhibit a remarkable diversity of bioactive molecules tailored to specific ecological roles. Due to their diversity, venom components exhibit a broad spectrum of envenomation effects by interacting with various molecular targets in host cells3. Consequently, venom toxins can induce diverse envenomation effects including haemotoxic, myotoxic, cytotoxic, and neurotoxic complications4. Despite their inherent toxicity, venoms have gathered significant interest in pharmacological research due to their clinical potential. Indeed, several toxins show promise in the treatment of various conditions such as pain, stroke, and cancer in humans5. Hence, a wider understanding of the composition, function, and evolutionary origin of venoms is crucial, not only for studying their roles in envenomings, but also for uncovering their untapped potential in biomedical applications. The advancement of biomedical technologies has revolutionised venom research in recent years by facilitating the identification and characterisation of numerous venom components6,7,8. The integrated omics approach empowered researchers to identify and characterise various molecules despite their low concentrations in venoms9. Several molecular studies provide better insights into the mechanism of actions of venom toxins and offer avenues for the development of venom-based therapeutic agents10. Like other naturally derived molecules, developing drug candidates from venoms requires careful structure-activity relationships and appropriate chemical modifications to mitigate potential toxicity while enhancing stability and bioavailability5. Moreover, the characterisation of venoms has a significant role in understanding and managing envenomation effects, particularly, snakebite envenoming (SBE). Notably, SBE has been classified as a high-priority neglected tropical disease and it poses a considerable burden on public health, especially in impoverished areas of the world11. It is estimated that between 1.8 and 2.7 million people worldwide suffer from SBE annually, leading to around 125,000 deaths and 400,000 permanent disabilities12. The clinical manifestations and pathophysiological effects of SBE vary widely depending on the species/family of snake involved13,14. Paralysis, respiratory failure, haemorrhage, coagulopathy, renal failure and tissue necrosis are some of the most common and medically significant envenomation effects in SBE victims15. The variability in venom compositions, the range of envenomation effects and the amount of venom injected necessitate robust preclinical evaluation to determine the efficacy of antivenoms16.

Considering the wide range of applications for venom research, this Collection invited articles that report recent advances in this field. A collection of articles published here provides novel insights into envenomation effects including local tissue damage and the development of diagnostic tools for corroborating envenomation in biological samples of bite victims. Here, we summarise the key take-home messages of the Collection.

Currently, there are no specific diagnostic tools available to ascertain envenomation, with treatment being provided based on the clinical symptoms that the patients manifest. Knudsen et al.17 address this gap in SBE management by developing a rapid diagnostic kit to detect the venoms of specific medically important snakes in Brazil. The monoclonal antibody-based lateral flow assay offers a promising solution for accurate and timely diagnosis of venoms in biological matrices, although this kit needs further testing in patient samples. When made available in the market, this kit will significantly improve patient outcomes, by supporting healthcare professionals in correctly diagnosing SBE and providing timely treatments, particularly in rural areas where SBE is more prevalent.

SBE-induced tissue damage is a serious condition which often leads to permanent disabilities. Therefore, it is important to further develop this niche area of research to determine the impact of venoms on various tissues in humans and develop better treatment strategies. Laprade et al.18 validated a machine learning guided tool (named ‘Venom Induced Dermonecrosis Analysis tooL-VIDAL’) to assess the severity of tissue damage using samples derived from animal models of envenoming. This tool offers a reliable and efficient method to analyse venom-induced tissue damage, which is an alternative to traditional histopathological analyses that are time-consuming and susceptible to human error. In turn, Haidar et al.19 examined the effects of Russell’s viper (Daboia russelii) and cobra (Naja naja) venoms on cultured myoblast cells. Russell’s viper venom reduces cell number, migration, and focal adhesion, while suppressing myogenic differentiation and inducing muscle atrophy. Cobra venom reduces viability and affects myotube formation, leading to atrophy. Importantly, cobra venom-induced atrophy is not reversed by certain inhibitors, although antivenom attenuates its effects. This study sheds light on the mechanisms underlying venom-induced muscle damage and highlights the need for further research to develop effective therapies for SBE-induced myotoxicity in vivo.

Naja nigricollis venom (NnV) contains complex toxins that affect various vital systems after envenomation. Adeyi et al.20 investigated the potential of kaempferol to mitigate NnV-induced male reproductive toxicity in rats. Results demonstrated that NnV significantly reduced hormone concentrations and sperm parameters in untreated rats, while also increasing oxidative stress biomarkers and causing severe morphological defects in reproductive organs. The kaempferol treatment normalised the hormone levels, improved sperm function, suppressed inflammatory and oxidative stress markers, and ameliorated histopathological lesions in envenomed rats. These findings support the potential of kaempferol against reproductive toxicity induced by SBE. Hiu et al.21 identified the T-cell and B-cell epitope sequences against a conserved cytotoxin of cobra venom (Naja sp.) using immunoinformatic tools and molecular docking simulation with different Human Leukocyte Antigens. By elucidating the epitope sequences crucial for the cytotoxicity of venom components, this research offers a promising avenue for the development of synthetic antigens to enhance antivenom efficacy.

Venom allergy, particularly induced by hymenopterans (bees, wasps, ants, and sawflies), causes high annual mortality, ranging from 0.03 to 0.45 per one million individuals22. Hymenoptera venom allergy is a severe condition characterised by anaphylactic reactions that can lead to death22. The anaphylactic reactions triggered by hymenopteran stings leading to life-threatening shock, typically occur within 15 min and require immediate administration of intramuscular epinephrine22. The diagnosis of this condition typically involves skin prick and intradermal tests, and/or measuring serum-specific IgE levels. While avoiding areas with high insect concentrations is the primary prevention method, it may not be feasible for certain professions like foresters or gardeners. Wasp venom immunotherapy (VIT) may offer a solution. VIT is a promising treatment for managing venom allergies by modifying the immune response to venom allergens. Previous studies have shown that VIT induces a shift in T helper cell responses from Th2 to Th1, marked by increased production of IL-2 and interferon-gamma23. Urbańska et al.24 measured serum concentrations of 30 cytokines in 61 patients affected with wasp venom hypersensitivity over 24 weeks to determine the long-term effects of VIT. While IL-2 and IFN-γ levels remained unchanged, there was a significant increase in IL-12 concentration, supporting its role in Th1 cell differentiation during VIT-induced desensitisation. Moreover, elevated levels of IL-9 and TGF-β suggest their involvement in generating regulatory T cells, potentially contributing to immune tolerance. Further research is needed to fully understand the mechanisms underlying VIT-induced desensitization.

Overall, the remarkable findings reported in this Collection not only deepen our understanding of venoms and their pathophysiology but also address some serious gaps in venom research. These studies inspire further advancements in venom research contributing to different fields, including clinical medicine, pharmacology, and toxicology. This will lead to further interdisciplinary research in this arena to develop better diagnostic methods for envenomings and treatment strategies for tacking specific envenomation effects such as allergy and skeletal muscle damage. Moreover, this Collection demonstrates the wide opportunities for scientific research on venoms.