Search Results (688)

Melittin, a cytolytic peptide derived from honeybee venom, has demonstrated potent anticancer activity through mechanisms such as membrane disruption, apoptosis induction, and modulation of key signaling pathways. Melittin exerts its anticancer activity by interacting with key molecular targets, including downregulation of the PI3K/Akt and NF-κB signaling pathways, and by inducing mitochondrial apoptosis through reactive oxygen species generation and cytochrome c release. However, its clinical application is hindered by its systemic and hemolytic toxicity, rapid degradation in plasma, poor pharmacokinetics, and immunogenicity, necessitating the development of targeted delivery strategies to enable safe and effective treatment. Nanoparticle-based delivery systems have emerged as a promising strategy for overcoming these challenges, offering improved tumor targeting, reduced off-target effects, and enhanced stability. This review provides a comprehensive overview of the mechanisms through which melittin exerts its anticancer effects and evaluates the development of various melittin-loaded nanocarriers, including liposomes, polymeric nanoparticles, dendrimers, micelles, and inorganic systems. It also summarizes the preclinical evidence for melittin nanotherapy across a wide range of cancer types, highlighting both its cytotoxic and immunomodulatory effects. The potential of melittin nanoparticles to overcome multidrug resistance and synergize with chemotherapy, immunotherapy, photothermal therapy, and radiotherapy is discussed. Despite promising in vitro and in vivo findings, its clinical translation remains limited. Key barriers include toxicity, manufacturing scalability, regulatory approval, and the need for more extensive in vivo validation. A key future direction is the application of computational tools, such as physiologically based pharmacokinetic modeling and artificial-intelligence-based modeling, to streamline development and guide its clinical translation. Addressing these challenges through focused research and interdisciplinary collaboration will be essential to realizing the full therapeutic potential of melittin-based nanomedicines in oncology. Overall, this review synthesizes the findings from over 100 peer-reviewed studies published between 2008 and 2025, providing an up-to-date assessment of melittin-based nanomedicine strategies across diverse cancer types. Full article

The white-spotted jellyfish, Phyllorhiza punctata, is an invasive species with significant ecological and economic relevance spreading across various regions. While its ecological impact is well-documented, its molecular and biochemical characteristics remain poorly understood. In this study, we integrate proteomic data generated by LC-MS/MS with publicly available transcriptomic information to characterize P. punctata, analyzing differential protein expression across three distinct tissues: oral arms, mantle, and gonads. A total of 2764 proteins and 25,045 peptides were identified, including several venom components such as jellyfish toxins (JFTs) and phospholipase A2 (PLA2), which were further investigated and compared to toxins from other species. Enrichment analyses revealed clear tissue-specific functions. Additionally, deep learning and machine learning tools identified 274 promising AMP candidates, including the α-helical, β-sheet, and αβ-motif peptides. This dataset provides new insights into the protein composition of P. punctata and highlights strong AMP candidates for further characterization, underscoring the biotechnological potential of underexplored cnidarian species. Full article

Ant venoms are rich sources of bioactive molecules, including peptide toxins with potent and selective activity on ion channels, which makes them valuable for pharmacological research and therapeutic development. Voltage-dependent potassium (Kv) channels, critical for regulating cellular excitability or cell cycle progression control, are targeted by a diverse array of venom-derived peptides. This study focuses on MYRTX_A4-Tb11a, a peptide from Tetramorium bicarinatum venom, which was previously shown to have a strong paralytic effect on dipteran species without cytotoxicity on insect cells. In the present study, we show that Tb11a exhibited no or low cytotoxicity toward mammalian cells either, even at high concentrations, while electrophysiological studies revealed a blockade of hKv1.3 activity. Additionally, Ta11a, an analog of Tb11a from the ant Tetramorium africanum, demonstrated similar Kv1.3 inhibitory properties. Structural analysis supports that the peptide acts on Kv1.3 channels through the functional dyad Y21-K25 and that the disulfide bridge is essential for biological activity, as reduction seems to disrupt the peptide conformation and impair the dyad. These findings highlight the importance of three-dimensional structure in channel modulation and establish Tb11a and Ta11a as promising Kv1.3 inhibitors. Future research should investigate their selectivity across additional ion channels and employ structure-function studies to further enhance their pharmacological potential. Full article

Phospholipase A1 (Ves a 1), a major toxin from Vespa affinis venom, poses significant risks to allergic individuals. Nevertheless, the epitope determinants of Ves a 1 have not been characterized. Thus, identifying its linear B-cell epitopes is crucial for understanding envenomation mechanisms. In this study, we predicted and identified B-cell epitopes EP5 and EP6 as potential candidates. EP5 formed an α-helix at the active site of Ves a 1, whereas EP6 adopted an extended loop conformation. Both synthetic peptides were synthesized and evaluated for their inhibitory effects using immune-inhibitory assays with polyclonal antibodies (pAbs) targeting both native (nVes a 1) and recombinant (rVes a 1) forms. The Ves a 1 polyclonal antibodies (pAb-nVes a 1 and pAb-Ves a 1) were produced, and their specificity binding to Ves a 1 was confirmed by Western blot. Next, ELISA inhibition assays showed that EP5 and EP6 significantly blocked pAb binding to both nVes a 1 and rVes a 1. Dot blot and Western blot assays supported these findings, particularly with stronger inhibition toward rVes a 1. Furthermore, enzymatic assays indicated that nVes a 1 and rVes a 1 retained phospholipase activity. Immunoinformatics docking showed that EP5 and EP6 specifically bind to a single-chain variable fragment antibody (scFv) targeting Naja naja PLA2. Molecular analysis revealed similar amino acid interactions to the template, suggesting effective paratope–epitope binding. These results support the potential of EP5 and EP6 for future diagnosis and therapy of V. affinis venom allergy. Full article

Animal venoms are complex biochemical secretions rich in highly potent and selective bioactive molecules, including peptides, enzymes, and small organic compounds. Once associated primarily with toxicity, these venoms are now recognized as a promising source of therapeutic agents for a wide range of medical conditions. This review provides a comprehensive analysis of the pharmacological potential of venom-derived compounds, highlighting their mechanisms of action, such as ion channel modulation, receptor targeting, and enzyme inhibition. Successful venom-derived drugs like captopril and ziconotide exemplify the translational potential of this biological arsenal. We discuss therapeutic applications in cardiovascular diseases, chronic pain, cancer, thrombosis, and infectious diseases, as well as emerging peptide candidates in clinical development. Technological advancements in omics, structural biology, and synthetic peptide engineering have significantly enhanced the discovery and optimization of venom-based therapeutics. Despite challenges related to stability, immunogenicity, and ecological sustainability, the integration of AI-driven drug discovery and personalized medicine is expected to accelerate progress in this field. By synthesizing current findings and future directions, this review underscores the transformative potential of animal venoms in modern pharmacotherapy and drug development. We also discuss current therapeutic limitations and how venom-derived compounds may address unmet needs in specific disorders. Full article

Crotoxin (CTX), the main toxin in Crotalus durissus terrificus venom, is a heterodimeric complex known for its antitumoral, anti-inflammatory, and immunomodulatory properties. In macrophages, CTX stimulates energy metabolism, pro-inflammatory cytokines, superoxide production, and lipoxin A₄ secretion while inhibiting macrophage spreading and phagocytosis. These effects are completely blocked by Boc-2, a selective formyl peptide receptors (FPRs) antagonist. Despite the correlation between FPRs and CTX-mediated effects, their involvement in mediating CTX entry into macrophages remains unclear. This study aimed to investigate the involvement of FPRs in CTX entry into monocytes and macrophages. For this, THP-1 cells were silenced for FPRs or treated with Boc-2. Results demonstrated that FPR-related signaling pathways, which influence macrophage functions such as ROS release, phagocytosis, and spreading, were reduced in FPR-silenced cells. However, even in the absence of FPRs, CTX was efficiently internalized by macrophages. These findings suggest that FPRs are essential for the immunomodulatory effects of CTX, but are not involved in CTX internalization. Full article

Parasitoid venom significantly influences host physiology and development. Our previous research identified high levels of insulin-binding protein IMP-L2 in the venom of Scleroderma guani. IMP-L2 may inhibit the insulin/insulin-like growth factor signaling (IIS) cascade by competitively binding insulin-like peptides (ILPs) with insulin receptor (InR). However, how to regulate IIS transduction is unclear. We speculate that venom-derived IMP-L2 may bind ILPs to inhibit IIS transduction. Consequently, we investigated the regulation of the IIS/TOR pathway by venom-derived IMP-L2. An expression analysis of IIS/TOR pathway genes across various developmental stages of Tenebrio molitor demonstrated that this pathway governs the entire developmental process. By examining gene expression before and after parasitism, we determined that S. guani predominantly inhibits TOR pathway signaling in T. molitor post-parasitism. Bioinformatics and expression analyses revealed that IMP-L2 is critically involved in Hymenoptera insects, exhibiting high expression in the venom apparatus, and is upregulated in response to S. guani parasitism factors. Additionally, recombinant IMP-L2 was produced via eukaryotic expression. Finally, the recombinant IMP-L2 was found to inhibit the TOR and IIS/TOR signaling pathways at early (6 h) and late (24 h) stages post-injection. Knockdown of IMP-L2 in S. guani parasitized T. molitor pupae, resulting in accelerated death of T. molitor. During parasitism, S. guani may suppress host growth and development by modulating the IIS/TOR signaling pathway through venom-derived IMP-L2, potentially affecting host lifespan. Full article

Toscana virus (TOSV) and Schmallenberg virus (SBV) are arthropod-borne viruses from the Bunyaviricetes class, posing significant human and animal health threats. TOSV, endemic to the Mediterranean region, is a notable human pathogen detected in various animals, suggesting potential zoonotic reservoirs. SBV emerged in Europe in 2011, affecting ruminants and causing reproductive issues, with substantial economic implications. The rapid spread of both viruses underscores the need for novel antiviral strategies. Host defense peptides (HDPs), particularly those derived from scorpion venom, are gaining attention for their antiviral potential. This study investigated pantinin-1 and pantinin-2 for their inhibitory activity against TOSV and SBV by plaque reduction assay, tissue culture infective dose (TCID₅₀) determination, and the analysis of M gene expression via qPCR. Both peptides exhibited potent virucidal activity, with IC₅₀ values of approximately 10 µM, depending on the specific in vitro cell model used. Additionally, the selectivity index (SI) values were favorable across all virus/cell line combinations, with particularly optimal results observed for pantinin-2. In human U87-MG neuronal cells, both peptides effectively blocked TOSV infection, a critical finding given the virus’s association with neurological conditions like encephalitis. The strong efficacy of these peptides against these viruses underscores the broader applicability of venom-derived peptides as promising antiviral agents, particularly in the context of emerging viral pathogens and increasing resistance to conventional therapeutics. Further studies are needed to optimize their antiviral potency and to assess their safety in vivo using animal models. Full article

Temporal lobe epilepsy (TLE) is a common drug-resistant form of epilepsy, often accompanied by cognitive and emotional disturbances, highlighting the urgent need for novel therapies. Scorpion Venom Heat-Resistant Synthetic Peptide (SVHRSP), isolated and synthetically derived from scorpion venom, has shown anti-epileptic and neuroprotective potential. This study evaluated the anti-epileptic effects of SVHRSP in a kainic acid (KA)-induced TLE rat model. Our results demonstrated that SVHRSP (0.81 mg/kg/day) reduced the frequency and severity of spontaneous seizures. Behavioral tests showed improved cognitive performance in the novel object recognition, object location, and T-maze tasks, as well as reduced anxiety-like behavior in the open-field test. Moreover, SVHRSP mitigated hippocampal neuronal loss and glial activation. Transcriptomic analysis indicated that SVHRSP upregulates genes involved in adhesion molecule-triggered and axon guidance pathways. Western blotting and immunofluorescence further confirmed that SVHRSP restored dendritic (MAP2), axonal (NFL), and synaptic (PSD95) marker expression, elevated the functionally important L1CAM fragment (L1-70), and increased myelin basic protein-induced serine protease activity responsible for L1-70 generation. Blockade of L1CAM expression diminished the neuroprotective effects of SVHRSP, suggesting a critical role for L1CAM-mediated synapse functions. This study is the first to reveal the therapeutic potential of SVHRSP in TLE via L1CAM-associated mechanisms. 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

For centuries, researchers have been fascinated by the composition of scorpion venom and its local and systemic effects on humans. During a sting, scorpions inject peptides and proteins that can affect immune cells and neurons. While the immune and nervous systems have been studied independently in the context of scorpion stings, here we reveal part of the mechanism by which Tityus serrulatus venom induces hyperalgesia in mice. Through behavioral, immune, imaging assays, and mice genetics, we demonstrate evidence of neuroimmune crosstalk during scorpion stings. Tityus serrulatus venom induced mechanical and thermal hyperalgesia in a dose-dependent manner, as well as overt pain-like behavior. The venom directly activated dorsal root ganglia neurons and increased the recruitment of macrophages and neutrophils, releasing pro-inflammatory cytokines TNF-α and IL-1β. Blocking TRPV1⁺ neurons, TNF-α, IL-1β, and NFκB reduced the mechanical and thermal hyperalgesia, overt pain-like behavior, and the migration of macrophages and neutrophils induced by Tityus serrulatus venom. Collectively, Tityus serrulatus venom targets primary afferent nociceptive TRPV1⁺ neurons to induce hyperalgesia through the recruitment of macrophages and neutrophils and the release of pro-inflammatory cytokines. Full article

The venom of Nemopilema nomurai jellyfish represents a promising source of bioactive compounds with potential pharmacological applications. In our previous work, we identified two novel angiotensin-converting enzyme (ACE)-inhibitory peptides—IVGRPLANG (896.48 Da) and IGDEPRHQYL (1227.65 Da)—isolated from N. nomurai venom hydrolysates via papain digestion. In this study, we conducted a detailed biochemical and computational characterization of these peptides. The IC₅₀ values were determined to be 23.81 µM for IVGRPLANG and 5.68 µM for IGDEPRHQYL. Kinetic analysis using Lineweaver–Burk plots revealed that both peptides act as competitive ACE inhibitors, with calculated inhibition constants (K_i) of 51.38 µM and 5.45 µM, respectively. To assess the structural stability of the ACE–peptide complexes, molecular dynamics simulations were performed. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses provided insights into complex stability, while interaction fraction analysis elucidated key bond types and residue–ligand contacts involved in binding. Furthermore, a network pharmacology approach was employed to predict therapeutic targets within the renin–angiotensin–aldosterone system (RAAS). Eleven target proteins were identified: IVGRPLANG was associated with REN, ACE, CTSB, CTSS, and AGTR2; IGDEPRHQYL was linked to REN, AGT, AGTR1, AGTR2, KNG1, and BDKR2. Molecular docking analyses using HADDOCK software (version 2.4) were conducted for all targets to evaluate binding affinities, providing further insight into the peptides’ therapeutic potential. Full article

A large majority of cone snails (a species in the genus Conus) are vermivorous (worm-hunting), but the diversity and bioactivity of their venom peptides remain largely unexplored. In this study, we report the first venom gland transcriptomes from two species in the Rhizoconus clade, Conus capitaneus and Conus mustelinus, and a new Conus miles transcriptome from a specimen collected in the Philippines. From the set of assembled sequences, a total of 225 C. capitaneus, 121 C. miles, and 168 C. mustelinus putative peptide toxin transcripts were identified, which were assigned to 27 canonical gene superfamilies in C. capitaneus and 24 in C. miles and in C. mustelinus. Most of these venom peptides are novel, and some exhibit new cysteine patterns. Clustering also revealed 12 putative novel gene superfamilies, highlighting the diversity of uncharacterized venom peptides in this group. The O1-, M-, O2-, and con-ikot-ikot superfamilies were the most abundant, while gene superfamilies such as D and G2 were highly expressed. Several hormone-like conopeptides were also identified in this study, revealing the vast diversity of conopeptides from the Rhizoconus species. Full article

Cone snails are a large group of marine gastropods that produce a complex mixture of toxic compounds to hunt prey and defend against predators. The majority of the venom comprises small toxic peptides named conotoxins, which target membrane receptors. In contrast, a smaller part of the venom contains larger proteins and conoproteins, which are thought to be involved in conotoxin maturation and the envenomation process, respectively. Interestingly, many species of cone snails contain conoporins, which are similar to actinoporins—pore-forming toxins found in sea anemones. These actinoporin-like proteins (ALPs) have recently been detected in many molluscan species, and only a few have been experimentally characterized. Due to being highly expressed in the venom gland of many cone snail species, conoporins are thought to play an important part in the envenomation process. Despite this, the exact function of conoporins is currently unknown. We propose several hypotheses aiming to elucidate their biological role. Full article