Search Results (167)

Fireflies, which predominantly prey on various mollusks such as small snails and slugs, are renowned for their unique bioluminescence. Firefly toxins—particularly Lucibufagins (LBGs), which target the α-subunit of the sodium–potassium pump protein (ATPα)—play a crucial role in their survival strategies. However, the types and functions of venom proteins in fireflies remain to be elucidated. In this study, transcriptome sequencing was employed on the larval head of Pyrocoelia analis larvae, through which transcripts encoding several putative venom proteins were identified, including phospholipase A1/A2, 5′-nucleotidase, cysteine-rich secretory proteins (CRISPs), and insulin-like peptides. Structural comparison revealed that venom proteins in fireflies exhibited high sequence and structural similarity with venom proteins from various venomous animals (e.g., snakes, scorpions, spiders, and cone snails). These venom proteins may exert synergistic effects through multiple mechanisms, such as neurotoxicity, metabolic interference, and cytotoxicity, thereby playing an essential role in mollusk predation and defense against predators. Our study not only analyzes the complexity and uniqueness of Py. analis venom proteins but also provides a robust foundation for further exploration of the ecological adaptability and evolutionary mechanisms of these venom proteins. Full article

Lancehead pitvipers, Bothrops snakes, or, popularly, “jararacas”, are common and broadly distributed in the Americas, especially in Brazil, where they are responsible for causing a high number of snakebite accidents. Their venoms are able to induce local and systemic effects, such as hemorrhaging, acute kidney failure, and shock, that can be fatal. Among the compounds of the venom are phospholipases A₂ (PLA₂s), which are abundant in some Bothrops species. PLA₂s can perform different activities during envenoming, such as neurotoxicity, myotoxicity, and cytotoxicity, among others, through the hydrolysis of the ester bond at the sn-2 position of phospholipids, producing free fatty acids and lysophospholipids. Although different PLA₂s can be classified into different PLA₂ groups and subgroups, according to structure, function, size, localization and Ca²⁺ dependence, they converge to be available in biotechnological and therapeutic applications, such as antiviral and antitumor, among others, being relevant molecules to be deeply studied. Here, we provide the state of the art of PLA₂s, found in snake venoms, focusing on Bothrops venoms, as well as their potential applications, beyond their inhibitors, that also receive attention due their importance in PLA₂ studies and diverse applications. Full article

The development of snake venom-loaded nanobiosystems based on smart biopolymers represents a promising therapeutic approach in several biomedical research fields. Specifically, the western diamondback rattlesnake (Crotalus atrox) contains various bioactive peptides and proteins with reported antitumor activity. This research aimed to establish a simplistic, facile and straightforward protocol for preparing chitosan-g-poly(N-vinylcaprolactam) nanoparticles containing C. atrox venom for potential use as a therapeutic nanocarrier against breast carcinoma cell lines. Herein, the physicochemical properties of venom-loaded nanoparticles were evaluated by FTIR, DLS, and SDS-PAGE. Also, the biological properties of both C. atrox venom and Cs-Venom NPs such as hemagglutination and hemolysis activity were evaluated in vitro. Finally, we evaluated their cytotoxic activity against two breast carcinoma cell lines (T-47D and MDA-MB-231). The most suitable formulation exhibited a hydrodynamic size of 222 nm, a ζ-potential of 42.0 mV and an encapsulation efficiency of 88.6%. C. atrox venom exhibited hemagglutination at concentrations >15 µg/mL but, no hemagglutination or hemolysis was observed for the CS-Venom NPs. Lastly, the IC50 of Cs-Venom NPs was determined for the T-47D and MDA-MB-231 cell lines, at 61.7 and 59.0 µg/mL, respectively. Thus, Cs-Venom NPs exhibit promising properties that can be considered a feasible alternative for developing controlled-release therapeutic systems. Full article

The genus Oxyuranus, which includes some of the most venomous snakes in the world, presents a complex venom composition with potent neurotoxic and procoagulant effects. This study provides a comparative proteomic analysis of the venom of Oxyuranus microlepidotus (Inland Taipan) and Oxyuranus scutellatus (Coastal Taipan), aiming to elucidate the molecular basis underlying their distinct toxicological profiles. Using high-resolution chromatographic fractionation and LC-MS/MS, we identified a core set of nine protein families shared between both species, including phospholipases A₂ (PLA₂), three-finger toxins (3FTx), natriuretic peptides (NTP), nerve growth factors (NGF), and prothrombin activators (PTA). O. microlepidotus venom exhibited greater diversity of 3FTxs and unique protein families, such as Waprin and 5′-nucleotidases, suggesting lineage-specific functional adaptations. Quantitative analysis revealed a greater relative abundance of PLA₂s in O. scutellatus (66%) compared to O. microlepidotus (47%), whereas 3FTXs were more prominent in O. microlepidotus (33% vs. 9%). These interspecific differences likely underlie the distinct clinical manifestations of envenomation and reflect evolutionary divergence in the venom composition. Our findings provide molecular insights into taipan venom complexity and highlight novel toxin candidates with potential biomedical applications in neurobiology, hemostasis, and anti-infective therapy. Full article

One of the main targets for snake venoms in animal and human organisms is the circulatory system. Mechanisms of circulatory system injury within the victim’s body include, among others, the direct effect of snake toxins on structures in blood vessel walls. The interaction of a toxin with cells and the extracellular matrix of the vessel wall may manifest as cytotoxicity, leading to cell death by necrosis or apoptosis, and damage to vascular wall structures. Such interactions may increase capillary permeability, promoting hemorrhage or edema, and may also induce alterations in vascular tone, resulting in changes in blood pressure. Snake toxins may also affect the growth, function, and regenerative ability of the endothelium, thus modulating angiogenesis; some toxins exert protective or anti-atherosclerotic effects. Toxins interacting with the vasculature may be classified as enzymes (phospholipases A₂, metalloproteinases, L-amino acid oxidases, and hyaluronidases), proteins without enzymatic activity (vascular endothelial growth factors, disintegrins, C-type lectins and snaclecs, three-finger toxins, etc.), peptides (bradykinin-potentiating peptides, natriuretic peptides, sarafotoxins), and low-molecular-weight substances. This review summarizes the data on the vascular effects, particularly on the blood vessel wall, exhibited by various classes and groups of snake toxins. Full article

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

Background/Objectives: Bioactive peptides derived from animal venoms, toxins, and secretions demonstrate considerable pharmacological potential for use in the management of diabetes mellitus—a highly prevalent metabolic disorder of substantial global health significance. This integrative review systematically evaluated the current evidence regarding the pharmacological mechanisms underlying the antidiabetic properties of these bioactive peptides. Methods: This study was guided by the research question “What are the mechanisms of action of peptides derived from animal venoms in modulating parameters associated with diabetes?” developed using the PECo framework. A comprehensive literature search was executed across Scopus, PubMed, and Web of Science, focusing on studies from the last five years. Out of 190 identified articles, 17 satisfied the inclusion criteria. Results: Twenty-eight distinct peptides were characterized, exhibiting structural diversity with 7–115 amino acid residues and molecular weights of 900–13,000 Da. These compounds were sourced from venomous taxa including sea anemones, marine snails, spiders, centipedes, scorpions, and snakes. Their antidiabetic mechanisms encompassed glucagon-like peptide-1 (GLP-1) receptor agonism, insulin receptor activation, potassium channel inhibition, glucose transporter type 4 (GLUT4) upregulation, and α-amylase inhibition. Sequence analyses revealed substantial homology among peptides with analogous mechanisms—notably Con-Ins and ILP-Ap04, plus SpTx1 and SsTx-4—suggesting that structural determinants underlie their functional characteristics. Toxicological evaluations of nine peptides demonstrated low-toxicity profiles despite originating from toxic venom, crucial for therapeutic development. Conclusions: These peptides exhibited exceptional pharmacological potency with effective doses in nanogram-to-nanomole per kilogram ranges. Collectively, our findings underscore the therapeutic potential of venom-derived peptides as innovative candidates for use in diabetes management. Full article

Acanthophis antarcticus, commonly known as the death adder, is a venomous Australian snake and a member of the Elapidae family. Due to its robust body and triangular head, it was historically misclassified as a viper. Its venom is known for neurotoxic, hemorrhagic, and hemolytic effects but displays low anticoagulant activity. Although key toxins such as three-finger toxins (3FTxs) and phospholipase A₂ (PLA₂) have been previously described, no study has integrated proteomic and functional analyses to date. In this study, we conducted a comprehensive characterization of A. antarcticus venom. Reverse-phase high-performance liquid chromatography (RP-HPLC) followed by LC-MS/MS enabled the identification of nine toxin families, with 3FTxs and PLA₂ as the most abundant. Less abundant but functionally relevant toxins included Kunitz-type inhibitors, CRISP, SVMP, LAAO, NGF, natriuretic peptides, and nucleotidases, the latter being reported here for the first time based on proteomic evidence. Hydrophilic interaction chromatography (HILIC) coupled with MALDI-TOF was used to analyze polar, non-retained venom components, revealing the presence of low-molecular-weight peptides (2–4 kDa). Functional assays confirmed the enzymatic activity of HYAL, PLA₂, and LAAO and, for the first time, demonstrated inhibitory activity on serine peptidases and fibrinogenolytic activity in the venom of this species. These findings expand our understanding of the biochemical and functional diversity of this venom. Full article

Leukemias and lymphomas are hematologic malignancies characterized by complex pathophysiological mechanisms and increasing global incidence. Despite advances in chemotherapy, immunotherapy, and targeted therapies, challenges such as drug resistance and relapse persist, necessitating novel therapeutic strategies. This review explores the cytotoxic potential of venoms derived from snakes, bees, and scorpions against leukemia and lymphoma cells. Numerous venom-derived components, such as L-amino acid oxidases (LAAOs), phospholipases A₂ (PLA₂s), and peptides like melittin, demonstrate selective antitumor activity through mechanisms involving oxidative stress, apoptosis induction, cell cycle arrest, and immunomodulation. These molecules exert their effects via mitochondrial pathways, caspase activation, and inhibition of pro-survival signaling cascades such as NF-κB and PI3K/Akt. Despite promising preclinical results, the clinical translation of these bioactive compounds remains limited due to challenges in standardization, delivery, and safety profiling. This review highlights recent advances in venom research, summarizes key molecular targets, and discusses future directions to harness venom-derived molecules as innovative therapies for hematological cancers. Full article

Background: Snake envenomation is a major public health issue in Nigeria, primarily due to bites from Echis ocellatus, Naja nigricollis, and Bitis arietans. Understanding their venom composition is essential for effective antivenom development. This study characterizes and compares the venom proteomes of these snakes using iTRAQ-based proteomics, focusing on key toxin families and their relative abundances. Methods: Venom samples were ethically collected from adult snakes, pooled by species, lyophilized, and stored for proteomic analysis. Proteins were extracted, digested with trypsin, and labeled with iTRAQ. Peptides were analyzed via mass spectrometry, and data were processed using Mascot and IQuant for protein identification and quantification. Results: E. ocellatus and B. arietans venoms had similar profiles, rich in C-type lectins, serine proteases, and phospholipase A₂s. These comprised 17%, 11%, and 5% in E. ocellatus and 47%, 10%, and 7% in B. arietans, with metalloproteinases dominating both (53% and 47%). In N. nigricollis, three-finger toxins (9%) were most abundant, followed by metalloproteinases (3%). All species shared four core protein families, with N. nigricollis also containing four uncharacterized proteins. Conclusions: This study highlights venom compositional differences, advancing snake venom biology and informing targeted antivenom development. Full article

The treatment of proctological conditions, including hemorrhoids, anal fissures, and perianal abscesses, is often complicated by bacterial infections, particularly those involving multidrug-resistant Escherichia coli. This study presents the synthesis, characterization, and biological evaluation of the newly designed synthetic peptide AMPEC4, inspired by cytotoxin 5 from Naja ashei snake venom. AMPEC4 demonstrated potent antimicrobial properties with MIC values of 100 and 200 µg/mL, effectively inhibiting biofilm formation (up to 84%) and eradicating the pre-formed biofilm by up to 35%. The antibacterial activity of AMPEC4 was further supported by a membrane permeabilization assay, demonstrating its capacity to disrupt bacterial membrane integrity in a dose-dependent manner. Furthermore, AMPEC4 significantly promoted fibroblast migration, a critical step in tissue regeneration, while exhibiting notable biocompatibility, as evidenced by the absence of hemolytic, cytotoxic, and genotoxic effects. By addressing both infection control and tissue regeneration, AMPEC4 represents a promising therapeutic strategy for managing chronic wounds, particularly in the challenging environment of the anorectal region. Its ability to target Escherichia coli reference and clinical strains while accelerating the wound-healing process underscores its potential for future clinical applications. Full article

Snakebite envenoming constitutes a significant global health issue, particularly in Africa, where venomous species such as Echis vipers and Dendroaspis mambas pose substantial risks to human health. This study employs a standardized venomics workflow to comprehensively characterize and comparatively quantify the venom composition of nine medically relevant snake species chosen from among the deadliest in Africa. Utilizing shotgun venom proteomics and venom gland transcriptomics, we report detailed profiles of venom complexity, highlighting the relative abundance of dominant toxin families such as three-finger toxins and Kunitz-type proteins in Dendroaspis, and metalloproteinases and phospholipases A₂ in Echis. We delineate here the relative abundance and structural diversity of venom components. Key to our proteomic approach is the implementation of Multi-Enzymatic Limited Digestion (MELD), which improved protein sequence coverage and enabled the identification of rare toxin families such as hyaluronidases and renin-like proteases, by multiplying the overlap of generated peptides and enhancing the characterization of both toxin and non-toxin components within the venoms. The culmination of these efforts resulted in the construction of a detailed toxin database, providing insights into the biological roles and potential therapeutic targets of venom proteins and peptides. The findings here compellingly validate the MELD technique, reinforcing its reproducibility as a valuable characterization approach applied to venomics. This research significantly advances our understanding of venom complexity in African snake species, including representatives of both Viperidae and Elapidae families. By elucidating venom composition and toxin profiles, our study paves the way for the development of targeted therapies aimed at mitigating the morbidity and mortality associated with snakebite envenoming globally. Full article

For the first time, two poly-histidine-poly-glycine peptides (pHpG-H5 and pHpG-H7) were identified as promising candidates for matrix metalloproteinase inhibitors. cDNAs encoding pHpG-H5 and pHpG-H7 peptides were isolated from the Atheris squamigera cDNA library constructed using oligo(dT)-primed reverse transcription. Deduced sequences of pHpG peptides were systematically organised and utilised as templates for synthesising chemical replicates. All synthetic pHpG peptides exhibited inhibitory effects on human matrix metalloproteinase-1 (MMP-1). Spectroscopic analyses and molecular modelling demonstrated that pHpG peptides disrupt zinc ion coordination within the central catalytic domain of MMP-1, thereby inhibiting its enzymatic activity. As a novel peptide inhibitor of matrix metalloproteinase, pHpG-H7 modulates multiple biological processes, such as cell migration and angiogenesis, suggesting significant therapeutic potential. Full article

The emergence of antimicrobial resistance is a significant challenge in global healthcare, necessitating innovative techniques to address multidrug-resistant pathogens. Multidrug-resistant pathogens like Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa pose significant public health threats, as they are increasingly resistant to common antibiotics, leading to more severe and difficult-to-treat infections. These pathogens are part of the ESKAPE group, which includes Enterococcus faecium, Staphylococcus aureus, and Enterobacter species. Animal venoms, derived from a wide range of species such as snakes, scorpions, spiders, bees, wasps, and ants, represent a rich source of bioactive peptides. Venoms have been a valuable source for drug discovery, providing unique compounds with therapeutic potential. Venom-derived drugs are known for their increased bioactivity, specificity, and stability compared to synthetic alternatives. These compounds are being investigated for various conditions, including treatments for diabetes, pain relief, cancer, and infections, showcasing their remarkable antimicrobial efficacy. In this review, we provide a comprehensive investigation into the potential of venom-derived compounds for developing new antimicrobial agents, including antibacterial, antifungal, antiviral, and antiparasitic therapeutics. Key venom components, including melittin from bee venom, phospholipase A₂ from snake venom, and chlorotoxin from scorpion venom, exhibit potent antimicrobial effects through mechanisms such as membrane disruption, enzymatic inhibition, and immune modulation. We also explore the challenges related to the development and clinical use of venom-derived antimicrobials, including toxicity, stability, and delivery mechanisms. These compounds hold immense promise as transformative tools against resistant pathogens, offering a unique avenue for groundbreaking advancements in antimicrobial research and therapeutic development. Full article

Current αIIbβ3 antagonists are potent antithrombotic agents, their clinical use is limited by the risk of life-threatening bleeding. Emerging evidence has highlighted key mechanistic differences between thrombosis and hemostasis, opening avenues for safer antithrombotic strategies. Targeting integrin αIIbβ3 outside-in signaling has been proposed to mitigate bleeding risk; however, the short half-life of peptide-based therapeutics remains a major challenge. In this study, we developed an optimized αIIbβ3 antagonist, KGDRR—a recombinant mutant protein derived from snake venom disintegrin, incorporating an Arg55 residue within the KGD loop—through systematic structure–activity relationship (SAR) analysis. Molecular docking revealed a critical cation–π interaction between Arg55 of KGDRR and Tyr122 of the β3 subunit, stabilizing integrin αIIbβ3 in an unliganded-closed conformation. Functionally, KGDRR selectively inhibited thrombus propagation by blocking ligand binding and downstream Gα13-mediated outside-in signaling while preserving initial thrombus core formation, which is a limitation of current αIIbβ3 inhibitors. Unlike conventional antagonists, KGDRR maintained αIIbβ3 in an unliganded-closed conformation without inducing the integrin activation and conformational change that lead to immune-mediated platelet clearance and thrombocytopenia. In animal models, KGDRR effectively suppressed thrombus growth without causing thrombocytopenia or prolonging bleeding time. Furthermore, intramuscular administration of KGDRR achieved a functional half-life 3.5 times longer than that of the clinically used antithrombotic eptifibatide at equivalent antithrombotic efficacy. In conclusion, KGDRR exhibits potent antithrombotic activity with a favorable safety profile and enhanced pharmacokinetic stability. These findings position KGDRR as a promising next generation αIIbβ3 antagonist with the potential to improve clinical outcomes in antithrombotic therapy. Full article