Spider Venom Research Articles

Unusual Complication of Breast Reconstruction by Prosthesis: Spider Bite by Loxosceles Rufescens

Unusual Complication of Breast Reconstruction by Prosthesis: Spider Bite by Loxosceles Rufescens

Efficient synthesis and anticancer evaluation of spider toxin peptide LVTX-8-based analogues with enhanced stability

Cytotoxic peptides derived from spider venoms have been considered as promising candidates for anticancer treatment. The novel cell penetrating peptide LVTX-8, which is a 25-residue amphipathic α-helical peptide isolated from spider Lycosa vittata, exhibited potent cytotoxicity and is a potential precursor for further anticancer drug development. Nevertheless, LVTX-8 may be easily degraded by multiple proteases, inducing the proteolytic stability problem and short half-life. In this study, ten LVTX-8-based analogs were rationally designed and the efficient manual synthetic method was established by the DIC/Oxyma based condensation system. The cytotoxicity of synthetic peptides was systematically evaluated against seven cancer cell lines. Seven of the derived peptides exhibited high cytotoxicity towards tested cancer in vitro, which was better than or comparable to that of natural LVTX-8. In particular, both N-acetyl and C-hydrazide modified LVTX-8 (825) and the conjugate methotrexate (MTX)-GFLG-LVTX-8 (827) possessed more durable anticancer efficiency, higher proteolytic stability, as well as lower hemolysis. Finally, we confirmed that LVTX-8 could disrupt the integrity of cell membrane, target the mitochondria and reduce the mitochondrial membrane potential to induce the cell death. Taken together, the structural modifications were conducted on LVTX-8 for the first time and the stability significantly improved derivatives 825 and 827 may provide useful references for the modifications of cytotoxic peptides.

Structure-based virtual screening to predict Loxosceles spider venom natural inhibitors

ObjectiveLoxosceles spider bite accidents are rising in wide areas of the world which necessitates the exploration of natural inhibitors to inhibit the most significant enzymes, namely sphingomyelinase D (Smase D) and hyaluronidase. MethodsVirtual screening using traditional Chinese medicine (TCM) against Smase D (PDB ID: 2F9R) and hyaluronidase was performed by the DrugRep server. Absorption, distribution, metabolism, and excretion (ADME) parameters were predicted via the same server. In addition, molecular dynamics (MD) simulation was conducted using CABS-flex 2.0 tool to prioritize the best potential natural inhibitors. ResultsTiliroside and Digitoxin were the best natural inhibitors from TCM to Smase D and hyaluronidase in terms of molecular docking and ADME parameters, while Digitoxin and β-carotene were the most potent inhibitors against hyaluronidase. MD simulations demonstrated the stability of the docked complexes. ConclusionIn-silico inhibition of Loxosceles spidervenom enzymes through TCM was demonstrated, which deserves wet-lab experimentation.

A bivalent remipede toxin promotes calcium release via ryanodine receptor activation

Multivalent ligands of ion channels have proven to be both very rare and highly valuable in yielding unique insights into channel structure and pharmacology. Here, we describe a bivalent peptide from the venom of Xibalbanus tulumensis, a troglobitic arthropod from the enigmatic class Remipedia, that causes persistent calcium release by activation of ion channels involved in muscle contraction. The high-resolution solution structure of φ-Xibalbin3-Xt3a reveals a tandem repeat arrangement of inhibitor-cysteine knot (ICK) domains previously only found in spider venoms. The individual repeats of Xt3a share sequence similarity with a family of scorpion toxins that target ryanodine receptors (RyR). Single-channel electrophysiology and quantification of released Ca2+ stores within skinned muscle fibers confirm Xt3a as a bivalent RyR modulator. Our results reveal convergent evolution of RyR targeting toxins in remipede and scorpion venoms, while the tandem-ICK repeat architecture is an evolutionary innovation that is convergent with toxins from spider venoms.

Development of a validated molecular analytical method to determine the viral safety of F(AB´)2 products: A novel application for a well-known technique

The immunotherapy agents derived from horses are biological products that allow the neutralization of clinically relevant immunogens, such as the SARS-CoV-2 virus that causes COVID-19, or the neutralization of toxins present in the venoms of snakes, spiders, and other poisonous animals. Due to their importance, detecting adventitious viruses in equine hyperimmune serum (raw material in industrial processes) is a critical step to support the safety of products for human use, and, in consequence, it is a requirement for commercialization and distribution. The safety of the finished product is based on three complementary approaches: (i) testing of the source material (horse serum) donations, (ii) release of the starting material (i.e., pool of horse serum) based on non-reactivity for a range of human infectious or pathogenic viruses, and (iii) validate (selected) steps of the manufacturing process for their capacity to inactivate and/or remove a wide range of viruses potentially present in the starting material. Orthogonal approaches to reduce viral contamination risk include implementing a reliable and validated system for detecting adventitious viruses. Thus, it is necessary to establish trustworthy and sufficiently sensitive analytical methods to evidence the lack of viruses to assure the safety of the therapeutic product. Therefore, in this research, an analytical method based on end-point Reverse Transcription Polymerase Chain Reaction (RT-PCR) was developed, implemented, and validated in hyperimmune equine serum samples to detect Venezuelan equine encephalitis virus, West Nile virus, and Rabies virus.

A Review on Genotoxic and Genoprotective Effects of Biologically Active Compounds of Animal Origin.

Envenomation by animal venoms remains a serious medical and social problem, especially in tropical countries. On the other hand, animal venoms are widely used as a source of biologically active compounds for the development of novel drugs. Numerous derivatives of animal venoms are already used in clinical practice. When analysing the mechanisms of action of animal venoms, attention is usually focused on the main target of the venom's enzymes and peptides such as neurotoxic, cytotoxic or haemorrhagic effects. In the present review, we would like to draw attention to the "hidden" effects of animal venoms and their derivatives in regard to DNA damage and/or protection against DNA damage. Alkaloids and terpenoids isolated from sponges such as avarol, ingenamine G or variolin B manifest the capability to bind DNA in vitro and produce DNA breaks. Trabectidin, isolated from a sea squirt, also binds and damages DNA. A similar action is possible for peptides isolated from bee and wasp venoms such as mastoparan, melectin and melittin. However, DNA lesions produced by the crude venoms of jellyfish, scorpions, spiders and snakes arise as a consequence of cell membrane damage and the subsequent oxidative stress, whereas certain animal venoms or their components produce a genoprotective effect. Current research data point to the possibility of using animal venoms and their components in the development of various potential therapeutic agents; however, before their possible clinical use the route of injection, molecular target, mechanism of action, exact dosage, possible side effects and other fundamental parameters should be further investigated.

Holistic profiling of the venom from the Brazilian wandering spider Phoneutria nigriventer by combining high-throughput ion channel screens with venomics.

Introduction: Spider venoms are a unique source of bioactive peptides, many of which display remarkable biological stability and neuroactivity. Phoneutria nigriventer, often referred to as the Brazilian wandering spider, banana spider or "armed" spider, is endemic to South America and amongst the most dangerous venomous spiders in the world. There are 4,000 envenomation accidents with P. nigriventer each year in Brazil, which can lead to symptoms including priapism, hypertension, blurred vision, sweating, and vomiting. In addition to its clinical relevance, P. nigriventer venom contains peptides that provide therapeutic effects in a range of disease models. Methods: In this study, we explored the neuroactivity and molecular diversity of P. nigriventer venom using fractionation-guided high-throughput cellular assays coupled to proteomics and multi-pharmacology activity to broaden the knowledge about this venom and its therapeutic potential and provide a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We coupled proteomics with ion channel assays using a neuroblastoma cell line to identify venom compounds that modulate the activity of voltage-gated sodium and calcium channels, as well as the nicotinic acetylcholine receptor. Results: Our data revealed that P. nigriventer venom is highly complex compared to other neurotoxin-rich venoms and contains potent modulators of voltage-gated ion channels which were classified into four families of neuroactive peptides based on their activity and structures. In addition to the reported P. nigriventer neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides for which their activity and molecular target remains to be determined. Discussion: Our findings provide a platform for studying the bioactivity of known and novel neuroactive components in the venom of P. nigriventer and other spiders and suggest that our discovery pipeline can be used to identify ion channel-targeting venom peptides with potential as pharmacological tools and to drug leads.

Spiders’ digestive system as a source of trypsin inhibitors: functional activity of a member of atracotoxin structural family

Spiders are important predators of insects and their venoms play an essential role in prey capture. Spider venoms have several potential applications as pharmaceutical compounds and insecticides. However, transcriptomic and proteomic analyses of the digestive system (DS) of spiders show that DS is also a rich source of new peptidase inhibitor molecules. Biochemical, transcriptomic and proteomic data of crude DS extracts show the presence of molecules with peptidase inhibitor potential in the spider Nephilingis cruentata. Therefore, the aims of this work were to isolate and characterize molecules with trypsin inhibitory activity. The DS of fasting adult females was homogenized under acidic conditions and subjected to heat treatment. After that, samples were submitted to ion exchange batch and high-performance reverse-phase chromatography. The fractions with trypsin inhibitory activity were confirmed by mass spectrometry, identifying six molecules with inhibitory potential. The inhibitor NcTI (Nephilingis cruentata trypsin inhibitor) was kinetically characterized, showing a KD value of 30.25 nM ± 8.13. Analysis of the tertiary structure by molecular modeling using Alpha-Fold2 indicates that the inhibitor NcTI structurally belongs to the MIT1-like atracotoxin family. This is the first time that a serine peptidase inhibitory function is attributed to this structural family and the inhibitor reactive site residue is identified. Sequence analysis indicates that these molecules may be present in the DS of other spiders and could be associated to the inactivation of prey trypsin (serine peptidase) ingested by the spiders.

The deep-rooted origin of disulfide-rich spider venom toxins.

Spider venoms are a complex concoction of enzymes, polyamines, inorganic salts and disulfide-rich peptides (DRPs). Although DRPs are widely distributed and abundant, their evolutionary origin has remained elusive. This knowledge gap stems from the extensive molecular divergence of DRPs and a lack of sequence and structural data from diverse lineages. By evaluating DRPs under a comprehensive phylogenetic, structural and evolutionary framework, we have not only identified 78 novel spider toxin superfamilies but also provided the first evidence for their common origin. We trace the origin of these toxin superfamilies to a primordial knot - which we name 'Adi Shakti', after the creator of the Universe according to Hindu mythology - 375 MYA in the common ancestor of Araneomorphae and Mygalomorphae. As the lineages under evaluation constitute nearly 60% of extant spiders, our findings provide fascinating insights into the early evolution and diversification of the spider venom arsenal. Reliance on a single molecular toxin scaffold by nearly all spiders is in complete contrast to most other venomous animals that have recruited into their venoms diverse toxins with independent origins. By comparatively evaluating the molecular evolutionary histories of araneomorph and mygalomorph spider venom toxins, we highlight their contrasting evolutionary diversification rates. Our results also suggest that venom deployment (e.g., prey capture or self-defense) influences evolutionary diversification of DRP toxin superfamilies.

Latarcins: Antimicrobial and cell-penetrating peptides from spider venom.

The venom of the ant spider Lachesena tarabaevi is reported to be rich in linear membrane active peptides[1]. Latarcins is a group of seven linear antimicrobial peptides found in the venom of this spider. We have recently studied this entire group of peptides to address the secondary state, membrane orientation and toxicity using circular dichroism (CD) spectroscopy, oriented CD (OCD), solid-state 31P-/15N-NMR and fluorescence spectroscopy[2]. Our results show that all peptides fold into an α-helical state in presence of lipids. OCD and NMR experiments show that these helices are either surface bound, tilted in the membrane or tend to aggregate in the lipid bilayer. The most tilted peptide, Ltc2a, shows indiscriminate membrane-toxicity and damages natural membranes (antimicrobial and hemolytic activity) as well as artificial membranes (vesicle leakage) where as the aggregating peptide, Ltc6a, shows no toxicity towards natural membranes but instead induces leakage of artificial lipid vesicles. Other latarcins (Ltc1, Ltc3a, Ltc4a and Ltc5a) show high activity and are selective in bacterial killing without causing bilayer disturbances. This result indicates that latarcins may have intracellular targets, and thus the ability of these peptides to enter cancer cells was also studied. In order to reduce the membrane toxicity, truncated latarcins (short latarcins, Sltc) were synthesized. Shorter latarcins turned out to be even less cytotoxic and highly cell-penetrating. These biophysical studies of latarcins and their shorter analogues on model membranes along with their influence on natural membranes will be presented.

Killer Knots: Molecular Evolution of Inhibitor Cystine Knot Toxins in Wandering Spiders (Araneae: Ctenidae).

Venom expressed by the nearly 50,000 species of spiders on Earth largely remains an untapped reservoir of a diverse array of biomolecules with potential for pharmacological and agricultural applications. A large fraction of the noxious components of spider venoms are a functionally diverse family of structurally related polypeptides with an inhibitor cystine knot (ICK) motif. The cysteine-rich nature of these toxins makes structural elucidation difficult, and most studies have focused on venom components from the small handful of medically relevant spider species such as the highly aggressive Brazilian wandering spider Phoneutria nigriventer. To alleviate difficulties associated with the study of ICK toxins in spiders, we devised a comprehensive approach to explore the evolutionary patterns that have shaped ICK functional diversification using venom gland transcriptomes and proteomes from phylogenetically distinct lineages of wandering spiders and their close relatives. We identified 626 unique ICK toxins belonging to seven topological elaborations. Phylogenetic tests of episodic diversification revealed distinct regions between cysteine residues that demonstrated differential evidence of positive or negative selection, which may have structural implications towards the specificity and efficacy of these toxins. Increased taxon sampling and whole genome sequencing will provide invaluable insights to further understand the evolutionary processes that have given rise to this diverse class of toxins.

Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates.

Brown spider envenomation results in dermonecrosis, characterized by an intense inflammatory reaction. The principal toxins of brown spider venoms are phospholipase-D isoforms, which interact with different cellular membrane components, degrade phospholipids, and generate bioactive mediators leading to harmful effects. The Loxosceles intermedia phospholipase D, LiRecDT1, possesses a loop that modulates the accessibility to the active site and plays a crucial role in substrate. In vitro and in silico analyses were performed to determine aspects of this enzyme's substrate preference. Sphingomyelin d18:1/6:0 was the preferred substrate of LiRecDT1 compared to other Sphingomyelins. Lysophosphatidylcholine 16:0/0:0 was preferred among other lysophosphatidylcholines, but much less than Sphingomyelin d18:1/6:0. In contrast, phosphatidylcholine d18:1/16:0 was not cleaved. Thus, the number of carbon atoms in the substrate plays a vital role in determining the optimal activity of this phospholipase-D. The presence of an amide group at C2 plays a key role in recognition and activity. In silico analyses indicated that a subsite containing the aromatic residues Y228 and W230 appears essential for choline recognition by cation-π interactions. These findings may help to explain why different cells, with different phospholipid fatty acid compositions exhibit distinct susceptibilities to brown spider venoms.

Completeness of notifications of accidents involving venomous animals in the Information System for Notifiable Diseases: a descriptive study, Brazil, 2007-2019.

to describe the completeness of notifications of accidents involving venomous animals held on the Notifiable Health Conditions Information System (SINAN), in Brazil and its macro-regions, from 2007 to 2019. we analyzed essential and non-mandatory fields for snakebite, spider bite and scorpion sting notifications, considering the following completeness categories: Excellent (≤5.0% incompleteness), Good (5.0% to 10.0%), Regular (10.0% to 20.0%), Poor (20.0% to ≤50.0%) and Very Poor (>50.0%). Proportional change in completeness between 2007 and 2019 was estimated. 1,871,462 notifications were investigated. The "localized manifestations", "systemic manifestations", "case classification", "case progression" and "zone of occurrence" fields had excellent or good completeness. Completeness was regular or poor for the "schooling" and "race/color" fields. The "occupation" field was predominantly poorly or very poorly filled in. There was a proportional worsening in completeness (PC<0) in most regions for the "zone of occurrence", "case progression" and "schooling" fields. completeness of most fields improved, although socioeconomic and occupational fields require more attention.

Comparison between a Phoneutria nigriventer toxin treatment and galantamine treatment in a memory deficit mouse model

Acetylcholine modulates circuits related to cognitive functions (attention, cognitive flexibility, memory, and social interaction). Consequences of low acetylcholine levels in cholinergic synaptic clefts include memory and sociability impairments. VAChT KDHET mice exhibit diminished vesicular acetylcholine transporter protein production, which could evoke low acetylcholine quantal release and memory and sociability issues. It has been demonstrated that the PhKv toxin, isolated from the Phoneutria nigriventer (Brazilian wandering spider) venom, inhibits the enzyme responsible for acetylcholine hydrolysis, acetylcholinesterase. This could result in acetylcholine remaining longer in the synaptic cleft, as well as alleviating cognitive problems caused by low levels of this neurotransmitter. Hence, here we intended to investigate VAChT KDHET mice cognitive deficits in a behavioral assay - the novel object recognition task - and examine the potential effect of the PhKv toxin in memory improvement of this mouse model. First, we noted that VAChT KDHET mice showed impaired object recognition memory. We also observed that these deficits, especially those related to short-term memory in the behavioral test, are sex-related. Subsequently, to assess the effects of PhKv toxin in object recognition memory, we injected PhKv or galantamine in VAChT KDHET mice and compared their performance in the novel object recognition task. We noted that mice treated with PhKv performed similarly to mice treated with galantamine or both vehicles in this behavioral assay. Finally, we observed that mice treated with both vehicles displayed memory improvements compared to non-treated (naive) mutant mice. Together, our results imply that PhKv may have an effect on memory improvement, which might be further explored to elucidate its mechanisms of action.

Cases caused by spider bite in Tripoli, Libya

Spiders Arachnida has a significant impact on the insect population due to their position as predators and their effect on the ecology. Although spiders contain venom glands, the majority of them do not bite humans or cause harm, with the exception of a few situations, and usually only when they are trapped, injured, or annoyed. Spider bites resulted in serious injuries. This recent study includes a review of verified instances of spider bites in two large dermatological facilities in Tripoli, Libya (Tripoli Central Hospital and Bair al-UstaMilad Hospital). Data from all patients with verified spider bites during the years 2014 and 2019 were gathered. The total cases were 251, with 152 female patients (60.6%) and 99 male patients (39.4%) in total. Age groups (20-29 years) are the most commonly affected by spider bites, followed by age groups (0-9 years). The affected patient's body portion was the lower part (thighs and legs) (n = 189, 75.3%), while one patient (0.4%) had a spider bite on the backside. Furthermore, this study depicts the geographical distribution of documented instances. The majority of patients (53%) were from Tripoli. However, the need for medical counsel and treatment compelled some patients from other places to go to the capital city. In general, western Tripoli has the lowest patient percentage incidence (5.5%). This research reveals that the incidence of spider bites is quite low in comparison to the Libyan population, which may be related to the country's very low registration of cases.

Hitchhiking spider: a case of unilateral vasculitis.

A 63-year-old man presented with two days of palpable purpura over the right anterior shin and calf with notable point tenderness on the distal mid-calf without any palpable deep abnormality. Localized right calf pain worsened with walking and was associated with headache, chills, fatigue, and low-grade fevers. A punch biopsy of the anterior right lower leg showed necrotizing neutrophilic vasculitis of superficial and deep vessels. Direct immunofluorescence showed non-specific focal granular deposition of C3 within vessel walls. Three days after presentation, a live spider was found and microscopically identified as a male hobo spider. The patient suspected the spider arrived via packages shipped from Seattle, Washington. The patient was treated with a prednisone taper with full resolution of his cutaneous symptoms. Given the unilaterality of his symptoms and otherwise unexplained etiology, the patient was diagnosed with acute unilateral vasculitis secondary to hobo spider bite. Microscopic examination is required for identification of hobo spiders. Although not deadly, there have been several reports of cutaneous and systemic reactions resulting from hobo spider bites. Our case illustrates the importance of considering hobo spider bites in areas outside of their native regions, as they are known to travel in packaged items.

Production and Functional Evaluation of Anti-Loxosceles Sera Raised by Immunizations of Rabbits with Mutated Recombinant Phospholipases-D.

Loxoscelism is the clinical condition triggered after the bite of spiders of the genus Loxosceles. The main species involved in accidents in South America are L. intermedia, L. laeta, and L. gaucho. The only specific treatment is the anti-Loxosceles serum produced with crude venoms. As phospholipases D (PLDs) trigger most of the effects observed in accidents, we developed and evaluated second-generation sera using mutated PLDs as antigens. Three isoforms of PLDs with site-directed mutations without biological activities were used for rabbit immunizations: D32A-E34A (L. gaucho), W230A (L. intermedia), and H12A-H47A (L. laeta). Sera were produced using crude venoms of three species of Loxosceles enriched with mutated recombinant PLDs (MIX) or using only mutated PLDs (REC). Immunizations stimulated the immune system from the second immunization with higher antibody production in the REC group. In vivo neutralization assays demonstrated that both sera reduced edema and dermonecrosis caused by Loxosceles intermedia crude venom. Follow-up of animals during the immunization protocols and in the neutralization assays demonstrated that the mutated proteins and the sera are safe. Results demonstrate the potential of using mutated recombinant PLDs in total or partial replacement of Loxosceles venoms in animal immunizations to produce anti-Loxosceles sera for treatments of Loxoscelism.

Systemic Loxoscelism, Less Frequent but More Deadly: The Involvement of Phospholipases D in the Pathophysiology of Envenomation.

Bites of Loxosceles spiders can lead to a set of clinical manifestations called loxoscelism, and are considered a public health problem in many regions. The signs and symptoms of loxoscelism are divided into cutaneous and systemic forms. The former is more frequent and includes signs of envenoming at the bite site or neighboring regions. Systemic loxoscelism, although much less frequent, is associated with complications, and can even lead to death. It may include intravascular hemolysis, acute renal failure, and thrombocytopenia. Loxosceles venoms are enriched with phospholipases D (PLDs), which are a family of isoforms found at intra-species and inter-species levels. Under experimental conditions, these enzymes reproduce the main clinical signs of loxoscelism, including an exacerbated inflammatory response at the bite site and dermonecrosis, as well as thrombocytopenia, intravascular hemolysis, and acute renal failure. The role of PLDs in cutaneous loxoscelism was described over forty years ago, when studies identified and purified toxins featured as sphingomyelinase D. More recently, the production of recombinant PLDs and discoveries about their structure and mechanism has enabled a deeper characterization of these enzymes. In this review, we describe these biochemical and functional features of Loxosceles PLDs that determine their involvement in systemic loxoscelism.

Stings on wings: Proteotranscriptomic and biochemical profiling of the lesser banded hornet (Vespa affinis) venom.

Distinct animal lineages have convergently recruited venoms as weaponry for prey capture, anti-predator defence, conspecific competition, or a combination thereof. Most studies, however, have been primarily confined to a narrow taxonomic breadth. The venoms of cone snails, snakes, spiders and scorpions remain particularly well-investigated. Much less explored are the venoms of wasps (Order: Hymenoptera) that are infamous for causing excruciating and throbbing pain, justifying their apex position on Schmidt's pain index, including some that are rated four on four. For example, the lesser banded wasp (V. affinis) is clinically important yet has only been the subject of a few studies, despite being commonly found across tropical and subtropical Asia. Stings from these wasps, especially from multiple individuals of a nest, often lead to clinically severe manifestations, including mastocytosis, myasthenia gravis, optic neuropathy, and life-threatening pathologies such as myocardial infarction and organ failure. However, their venom composition and activity remain unexplored in the Indian subcontinent. Here, we report the proteomic composition, transcriptomic profile, and biochemical and pharmacological activities of V. affinis venom from southern India. Our findings suggest that wasp venoms are rich in diverse toxins that facilitate antipredator defence. Biochemical and pharmacological assessments reveal that these toxins can exhibit significantly higher activities than their homologues in medically important snakes. Their ability to exert potent effects on diverse molecular targets makes them a treasure trove for discovering life-saving therapeutics. Fascinatingly, wasp venoms, being evolutionarily ancient, exhibit a greater degree of compositional and sequence conservation across very distant populations/species, which contrasts with the patterns of venom evolution observed in evolutionarily younger lineages, such as advanced snakes and cone snails.

Ameliorative effects of omega-lycotoxin-Gsp2671e purified from the spider venom of Lycosa praegrandis on memory deficits of glutamate-induced excitotoxicity rat model.

Memory impairment is one of the main complications of Alzheimer's disease (AD). This condition can be induced by hyper-stimulation of N-Methyl-D-aspartate receptors (NMDARs) of glutamate in the hippocampus, which ends up to pyramidal neurons determination. The release of neurotransmitters relies on voltage-gated calcium channels (VGCCs) such as P/Q-types. Omega-lycotoxin-Gsp2671e (OLG1e) is a P/Q-type VGCC modulator with high affinity and selectivity. This bio-active small protein was purified and identified from the Lycosa praegrandis venom. The effect of this state-dependent low molecular weight P/Q-type calcium modulator on rats was investigated via glutamate-induced excitotoxicity by N-Methyl-D-aspartate. Also, Electrophysiological amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input-output and Long-term potentiation (LTP) curves were recorded in mossy fiber and the amount of synaptophysin (SYN), synaptosomal-associated protein, 25kDa (SNAP-25), and synaptotagmin 1(SYT1) genes expression were measured using Real-time PCR technique for synaptic quantification. The outcomes of the current study suggest that OLG1e as a P/Q-type VGCC modulator has an ameliorative effect on excitotoxicity-induced memory defects and prevents the impairment of pyramidal neurons in the rat hippocampus.