Search Results (158)

Emerging tolerance of Schistosoma mansoni to praziquantel, the only drug available for schistosomiasis treatment, highlights the need for new therapeutic targets. Snake venoms contain pharmacologically active proteins and peptides that can decrease the viability of S. mansoni worms in vitro. Long non-coding RNAs (lncRNAs) play important roles in S. mansoni and are promising new therapeutic targets. However, new candidates still need to be identified, as only four S. mansoni lncRNAs have been functionally characterized to date. Therefore, we investigated lncRNA expression changes in S. mansoni following incubation with Bothrops venoms. Adult worms were incubated with eight venoms at a sublethal dose, and phenotypic parameters were evaluated. RNA-Seq was conducted on worms incubated with Bothrops jararacussu or Bothrops moojeni venoms, followed by Weighted Gene Co-expression Network Analysis for each sex. B. moojeni venom reduced all phenotypic measurements, while B. jararacussu reduced oviposition. Both venoms altered global gene expression, including lncRNAs. Females showed two lncRNA hub genes in two venom-associated co-expression modules, while males showed 61 lncRNA hub genes in nine venom-associated modules. RT-qPCR validated six out of seven selected hub lncRNAs in male worms. These results reveal the involvement of lncRNAs in S. mansoni gene expression modulation induced by Bothrops venoms and point to lncRNAs that should be prioritized in future functional studies, such as SmLINC121220-IBu, SmLINC152105-IBu and SmLNCA123831-IBu. Full article

Snake venoms are rich sources of molecules with pharmacological potential, with approximately 90% of their composition consisting of proteins and peptides responsible for their biological activities. These proteins are classified as enzymatic or non-enzymatic. Enzymatic proteins function as catalysts in regulatory chemical reactions, whereas non-enzymatic proteins, despite lacking catalytic activity, play essential roles in physiological processes. Lectins are non-enzymatic proteins of non-immune origin characterized by carbohydrate- and glycoprotein-binding domains, enabling their ability to agglutinate erythrocytes. C-type lectins and C-type lectin-like proteins are commonly found in snake venoms and are associated with hemostatic disturbances, particularly bleeding and coagulation disorders. This review provides a comprehensive analysis of studies published over the past decade on lectins isolated from snake venom, addressing their definitions, classifications, structural characteristics, and mechanisms of action, as well as their relevance in biotechnological applications. Although progress has been made in elucidating their pharmacological properties, most studies have focused on plant lectins. In contrast, research on snake venom lectins remains limited, particularly regarding their heterologous activities. This gap, especially compared to other venom-derived molecules, highlights the need to further expand research on this class of proteins. Full article

Background: Three-finger toxins (3FTxs) are a major axis of functional diversification in advanced snake venoms, with canonical paralytic activity mediated through muscle-type nicotinic acetylcholine receptors (nAChRs) and a broader set of non-nicotinic targets. This review integrates evidence bearing on coevolution between 3FTxs and target receptors, spanning toxin origin, diversification, receptor evolution, and ecological context. Methods: The synthesis draws on comparative genomic and transcriptomic studies of 3FTx gene-family evolution, codon-model analyses of selection, structural characterisation of toxin–receptor interfaces, and functional assays (including receptor-mimicking peptide binding) that link sequence variation to binding and toxicity. Results: Across lineages, 3FTx diversification is repeatedly structured by strong constraint on the disulphide-rich scaffold with accelerated change concentrated in solvent-exposed loops, alongside birth–death dynamics and exon/segment-level innovation that expand binding specificity. On the receptor side, resistance-associated variation is most intensively characterised for the nAChR α₁ orthosteric site and includes convergent, mechanistically distinct solutions such as electrostatic repulsion and glycosylation-mediated steric interference. Within the predominantly elapid systems currently examined, integrative datasets indicate that prey-selective binding and geographically variable susceptibility can arise from modest substitutions at toxin–receptor interfaces, but they also reveal substantial taxonomic and target-specific biases. Conclusions: Current evidence supports adaptive diversification in both toxins and receptors, while broader evolutionary interpretations are limited by uneven sampling and the frequent lack of matched toxin and receptor variants analysed within a common evolutionary framework. Development of predictive models will require joint pipelines linking genomics, structure-informed evolutionary inference, scalable functional assays, and explicit ecological network context. Full article

Snakebite envenoming remains a critical public health issue, and the molecular variability of venoms limits the cross-species efficacy of conventional antivenoms. Here, we conducted a comparative proteomic analysis of Bitis arietans venom to identify conserved peptide regions derived from enzymatic toxins and evaluate their potential relevance for complementary immunotherapeutic applications. Enzyme-enriched venom fractions were isolated through sequential affinity and ion-exchange chromatography and were subsequently characterized using fluorogenic FRET substrates and inhibitor assays. LC–MS/MS analysis identified 1099 proteins and revealed 36 conserved peptides within snake venom metalloproteinases (SVMPs), serine proteases (SVSPs), and phospholipase A₂ (PLA₂), particularly located near catalytic residues and structurally essential motifs such as the HExxHxxGxxH zinc-binding site in SVMPs, the His-Asp-Ser catalytic triad in SVSPs, and the Ca²⁺-binding loop in PLA₂, across Viperidae venoms. These conserved regions were also observed in homologous toxin isoforms from additional Viperidae genera, supporting the evolutionary conservation of key functional domains. While sequence conservation alone does not guarantee neutralization capacity, the identified regions represent strong candidates for structural epitope mapping and targeted antibody development. This study provides a peptide-level framework for advancing complementary antibody-based therapies designed to broaden cross-species toxin recognition, reduce antivenom dosage requirements, and improve clinical outcomes in snakebite envenoming. Full article

The growing global threat of antimicrobial resistance (AMR), particularly in cutaneous wound infections, represents a significant clinical and economic challenge. Biofilm formation by multidrug-resistant pathogens, such as Acinetobacter baumannii, often complicates healing and leads to therapeutic failure. Antimicrobial peptides (AMPs) are a promising alternative to conventional antibiotics due to their potent membrane-disrupting mechanism of action and lower propensity to induce resistance. Background/Objectives: This study aimed to evaluate the antibacterial, antibiofilm, and in vivo efficacy of four snake venom-derived cathelicidin-like peptides—Btn (15-34) and BotrAMP14 from Bothrops atrox, and Ctn (15-34) and CrotAMP14 from Crotalus durissus—against multidrug-resistant A. baumannii, Escherichia coli, and Pseudomonas aeruginosa clinical isolates from skin infections, with emphasis on A. baumannii, a WHO priority pathogen. Methods: Minimal Inhibitory Concentration (MIC), Minimal Bactericidal Concentration (MBC), and Minimal Biofilm Inhibitory Concentration (MBIC) were determined against A. baumannii, Escherichia coli, and Pseudomonas aeruginosa. Time-kill kinetics, hemolytic activity, and cytotoxicity assays were performed. A murine skin wound infection model was established to evaluate in vivo antibacterial efficacy and safety. Results: MIC/MBC values ranged from 0.78 to 25 µM against planktonic cells. In comparison, MBIC ranged from 1.56 to 12.5 µM against biofilms. BotrAMP14 eradicated A. baumannii within 4 min, while CrotAMP14 achieved bactericidal action in 20 min at 1.56 µM. Both peptides exhibited no hemolytic activity up to 128 µM and low cytotoxicity (IC₅₀ > 128 µM). In vivo, BotrAMP14 and CrotAMP14 demonstrated significant antibacterial activity at 24 h and 48 h post-infection, respectively, surpassing that of meropenem. Conclusions: These findings suggest that BotrAMP14 and CrotAMP14 are promising topical antimicrobial agents for managing multidrug-resistant skin infections and may help address the urgent need for alternative therapies against antibiotic-resistant pathogens. Full article

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