Scorpion Venom Peptide Research Articles

Unraveling neuroprotection with Kv1.3 potassium channel blockade by a scorpion venom peptide.

Voltage-gated potassium channels play a crucial role in cellular repolarization and are potential therapeutic targets in neuroinflammatory disorders and neurodegenerative diseases. This study explores Tityus bahiensis scorpion venom for neuroactive peptides. We identified the αKtx12 peptide as a potent neuroprotective agent. In SH-SY5Y cells, αKtx12 significantly enhances viability, validating its pharmacological potential. And in the animal model, we elucidate central nervous system (CNS) mechanism of αKtx12 through neuroproteomic analyses highlighting αKtx12 as a valuable tool for characterizing neuroplasticity and neurotropism, revealing its ability to elicit more physiological responses. The peptide's potential to promote cell proliferation and neuroprotection suggests a role in functional recovery from nervous system injury or disease. This research unveils the neuroactive potential of scorpion venom-derived αKtx12's, offering insights into its pharmacological utility. The peptide's impact on neuronal processes suggests a promising avenue for therapeutic development, particularly in neurodegenerative conditions.

Antimicrobial Potential of Scorpion-Venom-Derived Peptides.

The frequent and irrational use of antibiotics by humans has led to the escalating rise of antimicrobial resistance (AMR) with a high rate of morbidity-mortality worldwide, which poses a challenge to the development of effective treatments. A large number of host defense peptides from different organisms have gained interest due to their broad antibacterial spectrum, rapid action, and low target resistance, implying that these natural sources might be a new alternative to antimicrobial drugs. As important effectors of prey capture, defense against other animal attacks, and competitor deterrence, scorpion venoms have been developed as important candidate sources for modern drug development. With the rapid progress of bioanalytical and high throughput sequencing techniques, more and more scorpion-venom-derived peptides, including disulfide-bridged peptides (DBPs) and non-disulfide-bridged peptides (NDBPs), have been recently identified as having massive pharmacological activities in channelopathies, pathogen infections, and cancer treatments. In this review, we summarize the molecular diversity and corresponding structural classification of scorpion venom peptides with antibacterial, antifungal, and/or antiparasitic activity. We also aim to improve the understanding of the underlying mechanisms by which scorpion-venom-derived peptides exert these antimicrobial functions, and finally highlight their key aspects and prospects for antimicrobial therapeutic or pharmaceutical application.

Polyamidoamine dendrimer conjugated with novel scorpion venom peptide as a promising targeted delivery system for glioblastoma

Polyamidoamine dendrimer conjugated with novel scorpion venom peptide as a promising targeted delivery system for glioblastoma

Androcin 18−1, a novel scorpion-venom peptide, shows a potent antitumor activity against human U87 cells via inducing mitochondrial dysfunction

Scorpion venom is a potent natural source for antitumor drug development due to the multiple action modes of anticancer components. Although the sequence of Androcin 18−1 has been identified from the transcriptome profile of the scorpion venom Androctonus bicolor, its bioactivity remains unclear. In this study, we described the antitumor mechanism whereby Androcin 18−1 inhibits the proliferation and induces apoptosis by inducing cell membrane disruption, ROS accumulation, and mitochondrial dysfunction in human U87 glioblastoma cells. Moreover, Androcin 18−1 could suppress cell migration via the mechanisms associated with cytoskeleton disorganization and MMPs/TIMPs expression regulation. The discovery of this work highlights the potential application of Androcin 18−1 in drug development for glioblastoma treatment.

Short-Chained Linear Scorpion Peptides: A Pool for Novel Antimicrobials.

Scorpion venom peptides are generally classified into two main groups: the disulfide bridged peptides (DBPs), which usually target membrane-associated ion channels, and the non-disulfide bridged peptides (NDBPs), a smaller group with multifunctional properties. In the past decade, these peptides have gained interest because most of them display functions that include antimicrobial, anticancer, haemolytic, and anti-inflammatory activities. Our current study focuses on the short (9-19 amino acids) antimicrobial linear scorpion peptides. Most of these peptides display a net positive charge of 1 or 2, an isoelectric point at pH 9-10, a broad range of hydrophobicity, and a Grand Average of Hydropathy (GRAVY) Value ranging between -0.05 and 1.7. These features allow these peptides to be attracted toward the negatively charged phospholipid head groups of the lipid membranes of target cells, a force driven by electrostatic interactions. This review outlines the antimicrobial potential of short-chained linear scorpion venom peptides. Additionally, short linear scorpion peptides are in general more attractive for large-scale synthesis from a manufacturing point of view. The structural and functional diversity of these peptides represents a good starting point for the development of new peptide-based therapeutics.

Novel Scorpion Toxin ω-Buthitoxin-Hf1a Selectively Inhibits Calcium Influx via CaV3.3 and CaV3.2 and Alleviates Allodynia in a Mouse Model of Acute Postsurgical Pain.

Venom peptides have evolved to target a wide range of membrane proteins through diverse mechanisms of action and structures, providing promising therapeutic leads for diseases, including pain, epilepsy, and cancer, as well as unique probes of ion channel structure-function. In this work, a high-throughput FLIPR window current screening assay on T-type CaV3.2 guided the isolation of a novel peptide named ω-Buthitoxin-Hf1a from scorpion Hottentotta franzwerneri crude venom. At only 10 amino acid residues with one disulfide bond, it is not only the smallest venom peptide known to target T-type CaVs but also the smallest structured scorpion venom peptide yet discovered. Synthetic Hf1a peptides were prepared with C-terminal amidation (Hf1a-NH2) or a free C-terminus (Hf1a-OH). Electrophysiological characterization revealed Hf1a-NH2 to be a concentration-dependent partial inhibitor of CaV3.2 (IC50 = 1.18 μM) and CaV3.3 (IC50 = 0.49 μM) depolarized currents but was ineffective at CaV3.1. Hf1a-OH did not show activity against any of the three T-type subtypes. Additionally, neither form showed activity against N-type CaV2.2 or L-type calcium channels. The three-dimensional structure of Hf1a-NH2 was determined using NMR spectroscopy and used in docking studies to predict its binding site at CaV3.2 and CaV3.3. As both CaV3.2 and CaV3.3 have been implicated in peripheral pain signaling, the analgesic potential of Hf1a-NH2 was explored in vivo in a mouse model of incision-induced acute post-surgical pain. Consistent with this role, Hf1a-NH2 produced antiallodynia in both mechanical and thermal pain.

Yellow scorpion (Buthus sinidicus) venom peptides induce mitochondrial-mediated apoptosis in cervical, prostate and brain tumor cell lines.

Scorpion venoms are known to contain over 100,000 biologically active constituents. However, only a few of them have been studied. The major constituents of venom are proteins and peptides, which exhibit various biological and pharmacological properties, including anticancer activities. In the current study, the venom of yellow scorpions (Buthus sindicus) found in Sindh, Pakistan, was extracted and evaluated for its anti-cancer and anti-inflammatory activities. The crude venom showed a dose dependent inhibition of phagocyte oxidative burst from human whole blood cells (28.3% inhibition at highest tested concentration of 300 μg/mL). In-vitro cytotoxicity of crude venom was evaluated against human prostrate (PC3), cervical (HeLa) and neuroblastoma (U87-MG) cell lines, along with cytotoxicity against normal human fibroblast (BJ) cells. Crude venom was cytotoxic to all cell lines, with prominent inhibitory effect on PC3 cells. Crude venom was fractionated through RP-UPLC, resulted in fifteen fractions, followed by evaluation of their anticancer potential. Among all, the fraction I significantly (P < 0.001) reduced the cell viability of all three cancer cell lines, and exhibited insignificant cytotoxicity against normal cell line. Furthermore, the apoptotic cell death pathway was evaluated for crude venom, and fraction I, in most sensitive cell line PC3, by using flow-cytometry analysis. Both crude venom and its fraction I caused a mitochondrial-mediated apoptosis in prostate cancer cells (PC3). To the best of our knowledge, this is the first report of the anticancer and anti-inflammatory activity of venom of Pakistani yellow scorpions. Results indicate their therapeutic potential, and a case for further purification and validation studies.

Therapeutic effect and potential application of scorpion venom peptide

Scorpions has been existing on earth for hundreds of million years, and its venoms are mostly highly toxic and presents a deadly threat to people around the world. Scorpion venoms are highly complicated cocktails of bioactive components including proteins, amino acids, peptides, and other organic or inorganic molecules. Among them, the main active components are bioactive peptides called neurotoxins. Advancements in research on the toxic mechanisms of common scorpion toxins has found various therapeutic properties of several peptides on a large variety of diseases including different types of cancer and infections. Therefore, scorpion venoms may not only be a threat, but also a valuable source of novel drug components, especially therapeutic peptides. This research gives a brief introduction on scorpions and the components of its venoms, and focuses on presenting current knowledge on the medical effects of neurotoxins in scorpion venom, and potentials applications of the peptides in drug development.

Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity

The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD – human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117–1202 µM). The most active peptide was synthesized using solid phase peptide synthesis and tested for its antiviral activity against SARS-CoV-2 (Lineage B.1.1.7). On exposure to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD – hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD – hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.

P-343 - Targeting brain tumours with radiolabelled chlorotoxin, a scorpion venom peptide

P-343 - Targeting brain tumours with radiolabelled chlorotoxin, a scorpion venom peptide

Protective effect of scorpion venom oligopeptides in human umbilical vein endothelial cells under benzo(α)pyrene exposure

Inflammation and oxidative stress play pivotal role in the process of atherosclerosis. Scorpion venom is widely used as anti-cancer agent, however, the anti-inflammatory and antioxidant activities of scorpion venom peptides (SVPs) are rarely explored. In the current study, seven novel SVPs were isolated in a protective activity tracking isolation method in a cell model of benzo(α)pyrene (BaP)-induced human umbilical vein endothelial cells (HUVECs). The current study showed that SVP-1 [Tyr-Thr-Trp-Glu-Ala] significantly attenuated BaP-induced reactive oxygen species (ROS) over-production and inflammatory cytokines (IL-6, IL-1β, TNF-α, NO and PGE2) over-expression. Furthermore, SVP-1 attenuated BaP-induced adhesion molecules over-expression and inhibited the NF-κB and AhR signalling pathways activation. Collectively, the present study, for the first time, shows that SVPs inhibit the NF-κB and AhR signalling pathways in HUVECs under BaP-exposure, which strongly suggests the therapeutic potential of SVPs against atherosclerosis.

Scorpion Venom Peptide Smp24 Revealed Apoptotic and Antiangiogenic Activities in Solid-Ehrlich Carcinoma Bearing Mice

Scorpion venom contains various peptides that could be utilized to treat various diseases, including cancer. This study aimed to evaluate the anti-cancer activity of scorpion venom peptide (Smp24) using a solid Ehrlich Carcinoma (SEC) mice model. SEC model was established by subcutaneous transplantation of SEC cells into Swiss albino female mice afterward subcutaneous injection of the Smp24 peptide compared to 5-Fluorouracil (5-FU) as a standard drug. Various biochemical, hematological, histopathological, immunohistochemical, and molecular (western blotting and RT-PCR) assays were performed to evaluate the antitumor activity of Smp24. Results revealed that Smp24 peptide significantly reduced tumor volume. Interestingly, Smp24 peptide significantly restored normal body functions in cancer-treated groups by maintaining HB, RBC’s, and WBC’s levels, reducing the elevated serum ALT and AST, and increasing total protein and albumin as well as enhancing antioxidant status through reducing the level of MDA and NO and elevating GSH, SOD, and CAT levels. Moreover, it restored the normal morphology of the liver and kidney tissues and improved hematological parameters in cancer-treated animals. Smp24 induced apoptosis in SEC cells, through upregulation of caspase-3 and BAX and the downregulation of VEGF, Bcl-2, p53, PCNA, and Ki67. Moreover, results exhibited the apoptotic and antiangiogenic effects of Smp24 against SEC cancer cells. These findings supported our previous results about the anti-cancer efficacy of Smp24 and made it a good candidate for developing effective and safe anti-cancer agents.

Current Status of Peptide Medications and the Position of Active Therapeutic Peptides with Scorpion Venom Origin

: Peptides are highly potent, selective, and relatively safe therapeutics. Over the past two decades, natural peptides have been obtained, studied, and eventually approved by the Food and Drug Administration (FDA) due to advancements in identification, production, modification, and analytical technologies. Some peptide therapeutics has been derived from the venom gland of venomous animals, including snake, leech, lizard, snail, and scorpion. Scorpion was identified as a reservoir of important peptides with pharmaceutical properties. The scorpion uses these peptides for capturing prey and defense. However, their pharmacological properties in treating different diseases, including cardiac problems, autoimmune and infectious diseases, and diverse cancers, have been confirmed. Ion channel modifiers are the greatest components of the scorpion venom glands. Due to advances in proteomic and transcriptomic approaches, the identification of new scorpion venom peptides is steadily increasing. In this review, we tried to represent the current status of peptide medicines and describe the last peptide medications approved by FDA in 2022. Moreover, we will further explain potent peptides originating from scorpion venom, which have gone through important steps to be approved.

Scorpion venom peptide HsTx2 suppressed PTZ-induced seizures in mice via the circ_0001293/miR-8114/TGF-β2 axis

BackgroundDue to the complexity of the mechanisms involved in epileptogenesis, the available antiseizure drugs (ASDs) do not meet clinical needs; hence, both the discovery of new ASDs and the elucidation of novel molecular mechanisms are very important.MethodsBALB/c mice were utilized to establish an epilepsy model induced by pentylenetetrazol (PTZ) administration. The peptide HsTx2 was administered for treatment. Primary astrocyte culture, immunofluorescence staining, RNA sequencing, identification and quantification of mouse circRNAs, cell transfection, bioinformatics and luciferase reporter analyses, enzyme-linked immunosorbent assay, RNA extraction and reverse transcription–quantitative PCR, Western blot and cell viability assays were used to explore the potential mechanism of HsTx2 via the circ_0001293/miR-8114/TGF-β2 axis.ResultsThe scorpion venom peptide HsTx2 showed an anti-epilepsy effect, reduced the inflammatory response, and improved the circular RNA circ_0001293 expression decrease caused by PTZ in the mouse brain. Mechanistically, in astrocytes, circ_0001293 acted as a sponge of endogenous microRNA-8114 (miR-8114), which targets transforming growth factor-beta 2 (TGF-β2). The knockdown of circ_0001293, overexpression of miR-8114, and downregulation of TGF-β2 all reversed the anti-inflammatory effects and the influence of HsTx2 on the MAPK and NF-κB signaling pathways in astrocytes. Moreover, both circ_0001293 knockdown and miR-8114 overexpression reversed the beneficial effects of HsTx2 on inflammation, epilepsy progression, and the MAPK and NF-κB signaling pathways in vivo.ConclusionsHsTx2 suppressed PTZ-induced epilepsy by ameliorating inflammation in astrocytes via the circ_0001293/miR-8114/TGF-β2 axis. Our results emphasized that the use of exogenous peptide molecular probes as a novel type of ASD, as well as to explore the novel endogenous noncoding RNA-mediated mechanisms of epilepsy, might be a promising research area.Graphical

Emerging cures for cancer: peptides from scorpion and spider venom

Animal toxins have shown applicability in treatments of various diseases, here some investigations of scorpion and spider venom peptides as cancer treatments have been presented. Scorpion peptides are believed to have antitumor and analgesic effects and may present the potential to be applied in human medicine as a drug for cancer. Similarly, some spider peptides either directly or indirectly are also proved to regulate tumour cell growth and death. Mechanism involved includes promoting cell apoptosis to prevent translocation of cancer cells thus control tumour growth. Such effects make these peptides promising drug candidates for cancer treatment. All five of scorpion venom peptide drugs being approved by FDA for clinical treatment, from which remarkable treating outcomes have been observed when treating cancers. In this paper, general aspects of different scorpion venoms as well as their anticancer mechanism have been thoroughly analysed, from which the successful application of Buthus martensii Karsch analgesic peptide in treating carcinoma was elected as the representative case.

Antimicrobial peptides: natural or synthetic defense peptides against HBV and HCV infections.

According to the literature, treatment of HCV and HBV infections faces challenges due to problems such as the emergence of drug-resistant mutants, the high cost of treatment, and the side effects of current antiviral therapy. Antimicrobial peptides (AMPs), a group of small peptides, are a part of the immune system and are considered as an alternative treatment for microbial infections. These peptides are water-soluble with amphiphilic (hydrophilic and hydrophobic surfaces) characteristics. AMPs are produced by a wide range of organisms including both prokaryotic and eukaryotic cells. The antiviral mechanisms of AMPs include inhibiting virus entry, inhibiting intracellular virus replication, inhibiting intracellular viral packaging, and inducing immune responses. In addition, AMPs are a new generation of antiviral biomolecules that have very low toxicity for human host cells, particularly liver cell lines. AMPs can be considered as one of the most important strategies for developing new adjuvant drugs in the treatment of HBV and HCV infections. In the present study, several groups of AMPs (with a net positive charge) such as Human cathelicidin, Claudin-1, Defensins, Hepcidin, Lactoferrin, Casein, Plectasin, Micrococcin P1, Scorpion venom, and Synthetic peptides were reviewed with antiviral properties against HBV and HCV.

Molecular Characterization of a cDNA Encoding of an Anionic Cysteine-Free Antimicrobial Peptide From the Iranian Scorpion Odontobuthus Doriae Venom Glands

Background: The venom peptides from the scorpion fauna of Iran have been poorly characterized so far.&#x0D; Objectives: In this study, we identified a cDNA encoding of an anionic cysteine-free antimicrobial peptide from the Iranian yellow scorpion odontobuthus doriae (O.doriae).&#x0D; Methods: The cDNA sequence of an anionic antimicrobial-peptide (AMP) was determined from the venom gland cDNA library of Iranian yellow scorpion O.doriae and was named ODAMP5. This sequence was characterized by a software. Then, the structure and function of its putative peptide were predicted in a bioinformatics manner. The library was constructed from 6 scorpion venom glands. The cDNA related to ODAMP5 was isolated from one positive clone of the library.&#x0D; Results: The analysis of ODAMP5 reveals a 51-residue mature peptide with an anionic property that was stable in physiological states. ODAMP5 was similar to anionic peptide Aba-2 from Androctonus bicolor and according to its structure, it can be a member of helical structure AMPs with a new type of putative conserved domain. Putative ODAMP5 has a small size which makes it convenient for synthesis.&#x0D; Conclusion: Furthermore, we created a framework to express the ODAMP5 peptide for future biomedical and pharmacological studies. ODAMP5 may be a new suitable therapeutic strategy for bacterial infection among a few recognized scorpion venom peptides without disulfide bridges.&#x0D;

Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro.

Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the hepatoma cell line HepG2 has been reported earlier. However, its mode of action against HepG2 hepatoma cells remains unclear. In the current research, Smp24 was discovered to suppress the viability of HepG2 cells while having a minor effect on normal LO2 cells. Moreover, endocytosis and pore formation were demonstrated to be involved in the uptake of Smp24 into HepG2 cells, which subsequently interacted with the mitochondrial membrane and caused the decrease in its potential, cytoskeleton reorganization, ROS accumulation, mitochondrial dysfunction, and alteration of apoptosis- and autophagy-related signaling pathways. The protecting activity of Smp24 in the HepG2 xenograft mice model was also demonstrated. Therefore, our data suggest that the antitumor effect of Smp24 is closely related to the induction of cell apoptosis, cycle arrest, and autophagy via cell membrane disruption and mitochondrial dysfunction, suggesting a potential alternative in hepatocellular carcinoma treatment.

Antimicrobial activity of CT-K3K7, a modified peptide by lysine substitutions from ctry2459 - A Chaerilus tryznai scorpion venom peptide

Antimicrobial peptides (AMPs) have started to garner more interest as novel antimicrobial agents. The scorpion venom peptide ctry2459 was modified to CT-K3K7 by lysine substitutions at the 3rd and 7th positions to increase the cationic properties. We discovered that the modified peptides CT-K3K7 had improved antibacterial activity, higher thermal stability, as well as lower hemolytic activity. It can kill S. aureus and P. aeruginosa rapidly, and reduce the production of biofilm and live bacterial residues in biofilm in vitro. CT-K3K7 has also been demonstrated to decrease bacterial counts, abscess area, and inflammatory cell infiltration in the mouse subcutaneous abscess models that were duplicated by S. aureus and P. aeruginosa.CT-K3K7 has difficulty in inducing S. aureus and P. aeruginosa to develop drug resistance, which may be related to the bactericidal properties. CT-K3K7 increases cationic properties by lysine substitutions can increase the electrostatic force between the peptides and the bacterial surface, which can lead to an increase in bacterial membrane permeability and DNA binding.In conclusion, the modified peptide CT-K3K7 enhances the antimicrobial activity and can be a novel antimicrobial agent candidate for the treatment of infections by S. aureus and P. aeruginosa.

Scorpion Peptide Smp24 Exhibits a Potent Antitumor Effect on Human Lung Cancer Cells by Damaging the Membrane and Cytoskeleton In Vivo and In Vitro.

Smp24, a cationic antimicrobial peptide identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, shows variable cytotoxicity on various tumor (KG1a, CCRF-CEM and HepG2) and non-tumor (CD34+, HRECs, HACAT) cell lines. However, the effects of Smp24 and its mode of action on lung cancer cell lines remain unknown. Herein, the effect of Smp24 on the viability, membrane disruption, cytoskeleton, migration and invasion, and MMP-2/-9 and TIMP-1/-2 expression of human lung cancer cells have been evaluated. In addition, its in vivo antitumor role and acute toxicity were also assessed. In our study, Smp24 was found to suppress the growth of A549, H3122, PC-9, and H460 with IC50 values from about 4.06 to 7.07 µM and show low toxicity to normal cells (MRC-5) with 14.68 µM of IC50. Furthermore, Smp24 could induce necrosis of A549 cells via destroying the integrity of the cell membrane and mitochondrial and nuclear membranes. Additionally, Smp24 suppressed cell motility by damaging the cytoskeleton and altering MMP-2/-9 and TIMP-1/-2 expression. Finally, Smp24 showed effective anticancer protection in a A549 xenograft mice model and low acute toxicity. Overall, these findings indicate that Smp24 significantly exerts an antitumor effect due to its induction of membrane defects and cytoskeleton disruption. Accordingly, our findings will open an avenue for developing scorpion venom peptides into chemotherapeutic agents targeting lung cancer cells.