Search Results (230)

Animal venoms induce systemic inflammatory response syndrome through their interaction, inter alia, with pattern recognition receptors (PRRs) of the innate immune system. CD5 and CD6 are lymphoid members of the scavenger receptor cysteine-rich superfamily, endowed with PRR activity against microbial-associated molecular patterns (MAMPs) derived from bacteria, fungi, viruses and/or parasites. In this study, we aimed to investigate CD5 and CD6 interaction with cobra (Naja haje), scorpion (Androctonus australis) and honeybee (Apis mellifera) venoms. Binding assays revealed direct, dose-dependent and specific interaction of soluble human CD5 and CD6 receptors with protein nature components from the three venoms. Proteomic analysis identified venom nerve growth factor, basic phospholipase A2 (PLA2) and cobra venom factor, in cobra venom, and scorpion venom toxins targeting potassium (α-KTx 8.1) and sodium channels (Neurotoxin-1″ and G-TI) as potentially interacting components with CD5 and CD6. Further studies confirmed direct binding of bee venom main components, phospholipase A2 and melittin, to both soluble CD5 and CD6 receptors. Interestingly, in vitro PLA2 activity from cobra and bee venom was significantly reduced by both soluble CD5 and CD6 receptors. These findings broaden the PRR properties of CD5 and CD6 and support their potential involvement in envenomation pathophysiology. Full article

Scorpion neurotoxins are small peptides that target ion channels and offer opportunities for novel therapeutic discovery. This study analyzed the functional effects of the venom and toxins from the Costa Rican endemic scorpion, Tityus championi. Initially, crude venom was tested on different isoforms of voltage-gated sodium channels. Our findings revealed that the venom contains toxins that affect mammalian Na_V1.6 and Na_V1.7, as well as the cockroach BgNa_V1 channel. Increased currents through Na_V1.6 and BgNa_V1 channels were associated with bigger window currents and inhibition of inactivation. Decreased Na_V1.7 currents were associated with smaller conductance. Crude venom and TCh3 toxin inhibited action potential generation in invertebrate neurons expressing Na_V1.7-like channels. In these neurons, Tch2 and Tch4 toxins shifted voltage sensitivity to more negative potentials, ultimately widening the window current but decreasing channel availability. Conversely, Tch3 behaved as an inhibitory toxin, closing window currents and decreasing channel availability. Structural modeling showed that Tch3 adopts an αββ fold and binds the S3–S4 loop of Domain II in human Na_V1.7. These data show the diverse effects of scorpion venoms on channels and neurons, characterize its principal toxins, and show that Tch3 has therapeutic potential for pain relief. Full article

Peptides from scorpion venom, mainly in species such as Olivierus martensii (formerly Olivierus martensii Karsch, often designated BMK) (BmK) and Tityus serrulatus from the Buthidae family, show real promise as painkillers that skip opioids altogether. They work by hitting specific ion channels and dialing down inflammation. This review gathers information on their molecular setups: disulfide-bridged types and those without, weighing in at 3 to 10 kilodaltons (kDa). Structural features include motifs stabilized by cysteines. In pain signaling, they block voltage-gated sodium channels (NaV) such as NaV1.7 and NaV1.8; take the BmK analgesic–antitumor peptide (BmK-AGAP) for example. Additionally, scorpion venom heat-resistant peptide (SVHRP) reduces microglia activity. Tests on rodents using formalin injections, acetic acid writhing, and chronic constriction injury (CCI) setups reveal pain relief that depends on dose and stacks up to morphine. Pairings like AGAP with lidocaine decrease the effective dose by half. In terms of safety, therapeutic levels have low-toxicity with a median lethal dose (LD50) over 20 mg/kg. Issues crop up with immune responses, unintended targets, and differences in venom batches. Clinical information remains thin, so gaps persist. Engineered versions could change the game for neuropathic pain, inflammatory conditions, and cancer-related discomfort. Standardization plus Phase I studies would help move this forward. Full article

The endo-lysosomal channel TRPML2 regulates key processes like membrane trafficking and autophagy, which are hijacked by many RNA viruses during endocytic entry. However, the development of TRPML2-targeted therapeutics has been hindered by a notable lack of high-affinity and selective peptide-based activators. Scorpion venom peptides, honed by evolution for exceptional specificity toward diverse membrane ion channels, represent a promising, underexplored natural library for discovering novel pharmacological probes and drug leads. Here, we screened and identified seven candidate peptides interacting with TRPML2 using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of the Mesobuthus martensii venom. Based on molecular docking analysis, the top four candidates—MMTX, BmP05, BmTX1, and BmKK12—were selected for chemical synthesis, oxidatively cyclized to form their native disulfide-bridged conformations, and subsequently purified and characterized by analytical HPLC and MS. Calcium imaging confirmed that two of the four oxidized peptides, BmP05 and BmKK12, exhibited superior potency in inducing a sharp increase in Ca²⁺ influx. Crucially, BmP05 and BmKK12 demonstrated potent, concentration-dependent inhibition of Zika virus (ZIKV) replication at the RNA level at non-cytotoxic concentrations, whereas the weaker activators MMTX and BmTX1 did not. The current study first reports animal venom-derived peptides that function as specific TRPML2 agonists with concomitant antiviral activity. Together, our findings provide not only new molecular probes for dissecting TRPML2 biology but also a pioneering strategy for developing host-directed, broad-spectrum therapeutics against viruses dependent on endo-lysosomal entry. Full article

The scorpion family Buthidae, renowned for its neurotoxin-rich venoms, dominates toxinology, while non-buthid venoms remain largely unexplored. Here, we present a comprehensive proteomic and biochemical characterization of the Amazonian chactid scorpion Brotheas amazonicus venom (BamazV), with emphasis on molecular complexity, proteolytic processing, and peptide diversity. Using an integrative venomics approach that combines molecular mass-based fractionation, reversed-phase chromatography, high-resolution mass spectrometry, N-terminal sequencing, and functional and immunological analyses, we reveal an unexpectedly complex venom profile enriched in high-molecular-weight components and extensively processed peptides, with more than 40 venom peptides sequenced by MS/MS and Edman degradation. The data provide evidence for non-canonical proteolytic events, including the generation of peptides from precursor regions not classically associated with mature venom components. In contrast to the venom of Tityus serrulatus, BamazV displays a “hydrolase-rich, neurotoxin-poor” profile, featuring a catalytically active Group III phospholipase A₂ (BamazPLA₂), a highly active hyaluronidase, metalloproteases, low-mass peptides, and potassium channel toxins. Our results suggest a hydrolytic prey-subjugation strategy, and limited cross-reactivity with commercial antivenom highlighted its distinct structural landscape. Overall, this study advances the understanding of venom evolution and proteolytic diversification in underexplored scorpion lineages, positioning B. amazonicus as a valuable model for investigating alternative venom strategies and identifying novel biotechnological scaffolds. Full article

Venom is a key evolutionary innovation of venomous organisms in the long-term process of survival adaptation. As one of the oldest arthropods, scorpions produce venom rich in bioactive peptides that also constitute a valuable pharmacological resource. Omics-driven discovery and structural biology have expanded the peptide catalog and clarified structure–function principles across disulfide-bridged (DBPs) and non-disulfide-bridged peptides (NDBPs). Within this arsenal, ion-channel targeting neurotoxins predominantly modulate Nav, Kv, Calcium, Chloride, and TRP channels to achieve predation, defense, and competition. Owing to their unique mechanisms of action and significant therapeutic potential, scorpion venom peptides have attracted sustained interest as leads and scaffolds for drug development. This review synthesizes current knowledge of scorpion venom composition, with an emphasis on the pivotal role of neurotoxins, covering their molecular diversity, structural features, and modes of ion-channel modulation, as well as emerging applications in disease treatment. Full article

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen associated with healthcare-related infections and is of particular concern due to its high level of antibiotic resistance and its ability to form biofilms. The global emergence of carbapenem-resistant A. baumannii highlights the urgent need for alternative therapeutic strategies. This study investigated the antibacterial and antibiofilm activities of two scorpion venom-derived peptides, pantinin-1 and pantinin-2, against a reference strain and a clinical isolate of A. baumannii. We found that both peptides, in the non-cytotoxic concentration range, have strong bactericidal activity, showing a minimum inhibitory concentration (MIC) of 6.25 μM and 12.5 μM for pantinin 1 and 2, respectively. Scanning electron microscopy (SEM) analysis showed that the peptides cause extensive damage to the bacterial membrane. Furthermore, both peptides showed potent antibiofilm activity, inhibiting adhesion and maturation, arresting biofilm expansion, and reducing the expression of key biofilm-associated genes (bap, pgaA, and smpA). Altogether, these findings indicate that pantinin-1 and pantinin-2 act through a dual mechanism, combining bactericidal and antivirulence activities. Their strong efficacy at low micromolar concentrations, together with low cytotoxicity, underscores their potential as innovative therapeutic candidates against infections caused by carbapenem-resistant, biofilm-forming A. baumannii. 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

Scorpion venom toxins are important peptides being studied for their clinical significance. These peptides act by binding to ion channels in the membrane of nerve cells, causing the symptoms associated with scorpion stings (scorpionism). They principally affect the function of voltage-gated sodium channels (Nav) and are valuable for studying ion channels. Scorpions from the Buthidae family contain toxins that affect sodium channels and have a high affinity for mammalian channels. In this study, two sodium toxins isolated from the venom of the scorpion Centruroides hirsutipalpus, a member of the Buthidae family, were identified as belonging to the beta-type subfamily. These toxins were purified from whole venom using molecular exclusion, cationic-exchange, and reverse-phase chromatography techniques. Their molecular masses were determined using mass spectrometry, while their amino acid sequences were obtained by Edman degradation. A comparative analysis revealed that the sequences are identical to ChiNaBet60 and ChiNaBet50 toxins (now named Chirp7 and Chirp9, respectively) previously identified in the venom gland transcriptomics from C. hirsutipalpus. Furthermore, toxicity studies showed that these toxins were lethal to mammals. Electrophysiological analysis revealed that these peptides act as sodium channel–modulating toxins. In addition, interaction assays with antibodies were performed to analyze the structural determinants governing the binding mechanism. Full article

Scorpion venom is a rich source of diverse bioactive molecules with medicinal importance. While the venoms of many Buthidae scorpions have been extensively studied for their toxicity and therapeutic potential, Hottentotta judaicus scorpion venom (HjSV) remains poorly explored. In this study, using LC-ESI-MS, we show that HjSV has a complex composition. We find that HjSV has no significant cytotoxic effects on three human cancer cell lines, even at concentrations of up to 1000 µg/mL. However, it exerts a dose-dependent insecticidal effect against Drosophila melanogaster, a well-established genetic model organism, and two medically relevant mosquito species, Aedes albopictus and Culex pipiens. These findings highlight the venom’s selective activity and reveal a species-dependent susceptibility in insects, with mosquitoes being more sensitive than Drosophila. Furthermore, we show that at sub-lethal doses, HjSV alters D. melanogaster behavioral patterns, significantly reducing locomotor activity and increasing sleep duration. Altogether, our results provide new insights into the dual role of HjSV as both an insecticidal agent and behavioral modulator, shedding light on its ecological function in prey subduing and its potential application in pest control strategies. Full article

Background: Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder with limited treatment options. Emerging evidence reveals bidirectional crosstalk between gut and brain through inflammatory signaling, leading us to hypothesize that anti-neuroinflammatory agents may concurrently ameliorate intestinal inflammation. The scorpion venom-derived heat-resistant synthetic peptide (SVHRSP), a bioactive peptide initially identified in scorpion venom and subsequently synthesized by our laboratory, possesses neuroprotective, anti-inflammatory, and antioxidative activities. Its properties make SVHRSP a promising candidate for investigating the therapeutic potential of anti-neuroinflammatory strategies in mitigating intestinal inflammation. Methods: Using a chronic dextran sodium sulfate (DSS)-induced colitis model in wild-type and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice, along with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, we assessed SVHRSP’s effects on inflammation, histopathology, gut permeability, oxidative stress markers, and α7nAChR-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. Results: SVHRSP treatment significantly ameliorated colitis symptoms in wild-type mice by reducing inflammation, repairing histological damage, restoring gut barrier function, and attenuating oxidative stress, with these effects abolished in α7nAChR knockout mice. Mechanistically, SVHRSP activated JAK2/STAT3 signaling through α7nAChR engagement, suppressing proinflammatory cytokine production in macrophages. Conclusion: These results demonstrated that SVHRSP alleviated intestinal inflammation via α7nAChR-dependent JAK2/STAT3 activation. Combined with its known neuroprotective properties, our findings support the repurposing of this neuroactive peptide, SVHRSP, for treating intestinal inflammatory disorders. Full article

Scorpions are characterized by their venomous adaptations, including specialized stingers, and their ecological diversity. Some families, such as Buthidae, have medically significant species and their venoms possess a diverse array of chemicals. In Mexico, Centruroides suffusus and Centruroides vittatus coexist, with C. suffusus considered medically important due to its highly toxic venom. This study describes the metabolomic and microbiomic profiles of C. suffusus and C. vittatus. The metabolomic profiling (12 amino acids and 28 acylcarnitines) reveals significant differences between the two species, hinting at metabolic and ecological variations. Ornithine (ORN) and arginine (ARG) were the most abundant in C. vittatus, while tyrosine (TYR) was the most abundant amino acid molecule in C. suffusus. The microbiome analysis (by Next-Generation Sequencing of the 16S ribosomal gene) indicates similarities in gut bacteria composition between the two species (Phyla: Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, Proteobacteria and Tenericutes). Full article

Accurate detection of residual jellyfish venom is crucial for species identification and clinical management post-envenomation. We developed a highly specific immunoassay for Nemopilema nomurai venom using polyclonal antibodies (titer: 1:256,000). The established i-ELISA exhibited linear detection (0–20 ng/mL) with low variability (intra-plate CV: 0.77–2.78%; inter-plate CV: 2.25–5.17%). The kit demonstrated remarkable thermal stability (<15% signal decay after 6 days at 37 °C; detectable positivity through Day 9), suggesting >1-year shelf life at 4 °C. It showed significantly higher sensitivity for N. nomurai venom than venoms from Rhopilema esculentum, Chrysaora quinquecirrha, Cyanea melanaster, scorpions, or bees (p < 0.01). Validation in murine/human skin envenomation models and serum from systemically intoxicated mice confirmed the reproducibility and stability of residual toxins. This study developed a highly sensitive, specific, reproducible, and stable i-ELISA for Nemopilema nomurai venom, providing a methodological basis for creating diagnostic kits for marine envenomation. Full article

Scorpion venom is a rich source of bioactive compounds with significant potential for anticancer drug development. Its diverse molecular composition, including neurotoxins, antimicrobial peptides, and enzymes, provides a vast library for therapeutic innovation. Proteomic analyses have characterized venom composition in several species, while further functional assays have clarified their anticancer mechanisms. This review synthesizes current knowledge on scorpion venom-derived peptides with demonstrated anticancer activity, which selectively target ion channels, induce apoptosis, or disrupt tumor microenvironments. Where available, we highlight proteomic studies that have identified these components and discuss their structural features relevant to drug design. We also examine clinical applications and the challenges in translating venom peptides into therapies. The crucial and growing role of proteomics in this field, particularly for venom fractionation, component identification, and structural characterization, is critically evaluated. Full article

Scorpion venoms contain a wide range of toxins that interact with a variety of target molecules (ion channels, receptors and enzymes) associated with synaptic transmission, action potential propagation, cardiac function, hemostasis and other physiological systems. Scorpion toxins are also active towards bacteria, viruses, fungi and parasites. Such interactions make scorpion toxins useful lead molecules for developing compounds with biotechnological and therapeutic applications, and as tools for cell biology. In addition, scorpion toxins act as insectotoxins, with promising applications as insecticides. This review describes the range of scorpion toxins and discusses their usefulness for the development of insecticides and therapeutic drugs. Full article