Venom Research Articles

Voltage-Gated Sodium Channels: A Prominent Target of Marine Toxins.

Voltage-gated sodium channels (VGSCs) are considered to be one of the most important ion channels given their remarkable physiological role. VGSCs constitute a family of large transmembrane proteins that allow transmission, generation, and propagation of action potentials. This occurs by conducting Na+ ions through the membrane, supporting cell excitability and communication signals in various systems. As a result, a wide range of coordination and physiological functions, from locomotion to cognition, can be accomplished. Drugs that target and alter the molecular mechanism of VGSCs’ function have highly contributed to the discovery and perception of the function and the structure of this channel. Among those drugs are various marine toxins produced by harmful microorganisms or venomous animals. These toxins have played a key role in understanding the mode of action of VGSCs and in mapping their various allosteric binding sites. Furthermore, marine toxins appear to be an emerging source of therapeutic tools that can relieve pain or treat VGSC-related human channelopathies. Several studies documented the effect of marine toxins on VGSCs as well as their pharmaceutical applications, but none of them underlined the principal marine toxins and their effect on VGSCs. Therefore, this review aims to highlight the neurotoxins produced by marine animals such as pufferfish, shellfish, sea anemone, and cone snail that are active on VGSCs and discuss their pharmaceutical values.

S1615 Empagliflozin-Associated Pancreatitis: A Consideration for SGLT2 Inhibitors

Introduction: Empagliflozin is a drug in the new class of diabetic medications sodium-glucose cotransporter-2 (SGLT2) inhibitors, indicated for treating type 2 diabetes mellitus. The mechanism of action of empagliflozin is to reduce renal reabsorption of glucose and increase its urinary excretion. Although rare in occurrence (less than 0.1%), drug-induced acute pancreatitis (DIAP) should be considered an adverse effect in patients treated with SGLT2 inhibitors. We report a case of a 47-year-old man who presented with severe epigastric abdominal pain found to have DIAP in the setting of empagliflozin use. Case Description/Methods: 47-year-old man with a history of abdominal aortic aneurysm status after stent placement, hypertension, and type 2 diabetes mellitus presented with severe, epigastric abdominal pain, nausea and vomiting for 2 days duration. The patient denied a history of pancreatitis, consuming alcohol, narcotic use, recent trauma, surgical procedures, or exposure to venomous animals. The patient was admitted for management of pancreatitis. Social history was negative for smoking, alcohol ingestion or illicit drug use. Home medications included empagliflozin (initiated 2 months prior), atenolol, and hydrochlorothiazide (HCTZ). He had no significant family history. Vital signs were within normal limits on admission. On physical exam the epigastrium was tender to palpation. Laboratory workup revealed an elevated lipase of 220 mg/dL. Other laboratory findings were unremarkable, including no eosinophilia, triglyceride level of 123 mg/dL (drawn fasting 1 day after admission), normal electrolyte levels, and liver function tests. Abdominal computed tomography angiography was obtained to evaluate the aortic stent and the pancreas, which revealed fat stranding and pancreatic inflammation in the head of the pancreas (Figure 1). Conservative treatment was initiated included intravenous hydration and pain management. Empagliflozin was held and discontinued on discharge. The patient has not had any further episodes of pancreatitis or gastrointestinal complaints at the 2-month outpatient follow-up. Discussion: As mentioned above, our patient had been started on empagliflozin therapy approximately 60 days before presentation. We believe that this timeframe further supports the likelihood of a causal relationship. This case demonstrates that SGLT2 inhibitors, although a rare cause, should be considered an important part of a clinician's differential when other common etiologies of pancreatitis have been excluded.Figure 1.: Abdominal computed tomography angiography—pancreatic fat stranding around the head of the pancreas consistent with acute pancreatitis (white arrow). Normal gallbladder without the presence of gallstones (red arrow).

Isolasi dan Karakterisasi Fungi Endofit Umbi Porang (Amorphophallus muelleri Blume) sebagai Antibakteri

Medicinal plants such as porang (Amorphophallus muelleri Blume) can produce bioactive compounds from plants-associated endophytes. Therefore, medicinal plants were a sources of isolation of endophytic fungi and endophytic fungi were a sources of secondary metabolites that have anticancer, antimalarial, antimicrobial, and so on. A Porang tuber has been used as a medicine for boils, medicine for sliced wounds and medicine for wounds due to venomous animal bites. The research was aimed to carry out isolation and characterization of endophytic fungi from porang tuber, and to test the ability of endophytic fungi from porang tuber as antibacterial against gram positive (Staphylococcus aureus) and gram negative (Escherichia coli) bacteria. Isolation of endophytic fungi from porang tubers succeeded in getting five different fungi isolates. Based on macroscopic and microscopic characteristics, endophytic fungi isolated from porang tuber were members of the genus Curvularia, Penicillium, 2 isolates of Aspergillus, and 1 isolate that had not been identified. Porang endophytic fungi had antibacterial activity against S. aureus, but did not have antibacterial activity against E. coli bacteria. Endophytic fungi that had antibacterial activity were Curvularia sp., Penicillium sp., Aspergillus sp.

Bioactive Molecules Derived from Snake Venoms with Therapeutic Potential for the Treatment of Thrombo-Cardiovascular Disorders Associated with COVID-19.

As expected, several new variants of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) emerged and have been detected around the world throughout this Coronavirus Disease of 2019 (COVID-19) pandemic. Currently, there is no specific developed drug against COVID-19 and the challenge of developing effective antiviral strategies based on natural agents with different mechanisms of action becomes an urgent need and requires identification of genetic differences among variants. Such data is used to improve therapeutics to combat SARS-CoV-2 variants. Nature is known to offer many biotherapeutics from animal venoms, algae and plant that have been historically used in traditional medicine. Among these bioresources, snake venom displays many bioactivities of interest such as antiviral, antiplatelet, antithrombotic, anti-inflammatory, antimicrobial and antitumoral. COVID-19 is a viral respiratory sickness due to SARS-CoV-2 which induces thrombotic disorders due to cytokine storm, platelet hyperactivation and endothelial dysfunction. This review aims to: (1) present an overview on the infection, the developed thrombo-inflammatory responses and mechanisms of induced thrombosis of COVID-19 compared to other similar pathogenesis; (2) underline the role of natural compounds such as anticoagulant, antiplatelet and thrombolytic agents; (3) investigate the management of coagulopathy related to COVID-19 and provide insight on therapeutic such as venom compounds. We also summarize the updated advances on antiviral proteins and peptides derived from snake venoms that could weaken coagulopathy characterizing COVID-19.Graphic

Cell affinity screening combined with nanoLC-MS/MS based peptidomics for identifying cancer cell binding peptides from Bufo Bufo gargarizans

Animal venoms contain many peptides with high specificity and selectivity against their protein targets, a characteristic which makes venoms an invaluable source of potential drugs. High-sensitivity mass spectrometry (MS)- based peptidomic platform has evolved as a predominant method for natural peptide drug discovery due to its strength for direct and rapid identification of peptides and peptide-associated post-translational modifications (PTMs). In this study, we used cell-affinity assays combined with nanoLC-MS/MS based peptidomics to identify cancer cell binding peptides (CBPs) from Bufo Bufo gargarizans. We identified 76 potential cell binding peptides and 237 non-affinity peptides in venom extracts from Asiatic toads, and some were verified with MS-parallel reaction monitoring (PRM) mode. These peptides were further analyzed and internalized within human cells and some demonstrated anti-tumor properties in vitro. These specific peptides might be used as templates for peptide-based drug design or optimization.

Changing Caribbean geographies: connections in flora, fauna and patterns of settlement from Indian inheritances

There can be no doubt that Indian immigration to the plantation colonies changed the geography of those colonies. However, most analyses have dealt with the sugar industry in the colonies after the abolition of slavery. This paper will argue that, apart from the sugar industry, Indian labour and ingenuity made other significant contributions to plantation economies. The girmityas (agreement signers) were well aware that they were going to agricultural occupations so they took with them an amazing array of dried fruits, seeds and cuttings, which survived the long crossing, adding to the flora of the plantations. Armed with this foreknowledge, the jahajis packed these items into their jahaji bundles alongside the Tulsi Ramayan and the Holy Qu'ran. Animals too formed part of this international trade. Sheep, goats and poultry which were not eaten on the outward voyage were sent to the estates, where they multiplied. When dangerous snakes threatened plantation security, cages of mongoose were dispatched to the Caribbean where they bravely tackled venomous creatures. At the urging of Indian labourers with long experience in the sugar industry, the plantations' owners imported Brahma bulls and Zebu cattle, which revolutionised transport on the estates and provided leather, manure and meat to the wider population. There is also the amazing story of the importation of hundreds of water buffaloes (bhaisa) from the Indo-Gangetic plains. Some nine breeds were imported and in the twentieth century Caribbean bio-geneticists were able to blend the best qualities of those Indian animals and created a new hybrid, the buffalypso, which combined the scientific name with Trinidad's fame as the land of the calypso. The buffalypso became a prized animal for haulage, meat, milk and leather and an item of export to Venezuela, Colombia, Miami and the wider Caribbean. Indian cultivars were continuously exported to the botanic gardens in the Caribbean and Indian forestry experts were sent to the region to advise on forest rehabilitation in the wake of large-scale deforestation, which sugar cultivation required. In these and other ways the physical character of the Caribbean underwent permanent change, which manifests itself today.

Pectoral-fin glands and delivery apparatus in the catfish genus Brachyrhamdia Myers, 1927 (Siluriformes: Heptapteridae)

The Siluriformes, popularly known as catfishes, are probably the vertebrate group with the highest diversity of venomous animals, even though only approximately a hundred venomous catfishes are reported to date. Venomous catfishes might present a delivery system apparatus, formed by an unbranched ray at the leading edge of pectoral and dorsal fins (spine), which can be stiffened and pungent, while venom glands can be present at the surface of such spines and/or the axillary region. This work investigated the presence, morphology and distribution of glands and pectoral-fin delivery apparatus in the heptapterid Brachyrhamdia genus. Pectoral-fin spine external morphology was compared across all valid species in the genus, histological sections of the pectoral-fin spine and axillary regions of B. heteropleura and B. marthae were produced, and dissections of the pectoral girdle region of the mentioned species were analyzed. The histological sections confirmed the presence of pectoral-fin glands at the surface of the pectoral-fin spine of Brachyrhamdia species, and cellular morphology indicates these glands are probably venomous. Also, we found a piriform gland at the axillary region, whose cell morphology is like the reported for other catfishes. However, we cannot currently confirm or deny axillary gland participation in the venom delivery apparatus. This work constitutes the first report of venom glands in Brachyrhamdia, and the first description of Heptapteridae axillary glands.

Origin and Characterization of Extracellular Vesicles Present in the Spider Venom of Ornithoctonus hainana.

Extracellular vesicles (EVs), including exosomes and microvesicles, are membranous vesicles released from nearly all cellular types. They contain various bioactive molecules, and their molecular composition varies depending on their cellular origin. As research into venomous animals has progressed, EVs have been discovered in the venom of snakes and parasitic wasps. Although vesicle secretion in spider venom glands has been observed, these secretory vesicles’ origin and biological properties are unknown. In this study, the origin of the EVs from Ornithoctonus hainana venom was observed using transmission electron microscopy (TEM). The Ornithoctonus hainana venom extracellular vesicles (HN-EVs) were isolated and purified by density gradient centrifugation. HN-EVs possess classic membranous vesicles with a size distribution ranging from 50 to 150 nm and express the arthropod EV marker Tsp29Fb. The LC-MS/MS analysis identified a total of 150 proteins, which were divided into three groups according to their potential function: conservative vesicle transport-related proteins, virulence-related proteins, and other proteins of unknown function. Functionally, HN-EVs have hyaluronidase activity and inhibit the proliferation of human umbilical vein endothelial cells (HUVECs) by affecting the cytoskeleton and cell cycle. Overall, this study investigates the biological characteristics of HN-EVs for the first time and sheds new light on the envenomation process of spider venom.

A Pseudoscorpion's Promising Pinch: The venom of Chelifer cancroides contains a rich source of novel compounds

With pedipalps modified for venom injection, some pseudoscorpions possess a unique venom delivery system, which evolved independently from those of other arachnids like scorpions and spiders. Up to now, only a few studies have been focused on pseudoscorpion venom, which either identified a small fraction of venom compounds, or were based on solely transcriptomic approaches. Only one study addressed the bioactivity of pseudoscorpion venom. Here, we expand existing knowledge about pseudoscorpion venom by providing a comprehensive proteomic and transcriptomic analysis of the venom of Chelifer cancroides. We identified the first putative genuine toxins in the venom of C. cancroides and we showed that a large fraction of the venom comprises novel compounds. In addition, we tested the activity of the venom at specific ion channels for the first time. These tests demonstrate that the venom of C. cancroides causes inhibition of a voltage-gated insect potassium channel (Shaker IR) and modulates the inactivation process of voltage-gated sodium channels from Varroa destructor. For one of the smallest venomous animals ever studied, today's toolkits enabled a comprehensive venom analysis. This is demonstrated by allocating our identified venom compounds to more than half of the prominent ion signals in MALDI-TOF mass spectra of venom samples. The present study is a starting point for understanding the complex composition and activity of pseudoscorpion venom and provides a potential rich source of bioactive compounds useable for basic research and industrial application.

P–801 Effects of Lonomia obliqua venom components on human endometrial stromal cells: A potential source for new cytoprotective biomolecules against recurrent pregnancy loss

Abstract Study question Could new molecules like Lonomia obliqua lipocalins and hemolins have cytoprotective effects on endometrial stem cells (hESC)? Summary answer Lonomia obliqua venom-induced hESC viability, proliferation and migration occurred mainly by protection against oxidative damage and ERK-dependent pathway activation What is known already Recurrent pregnancy loss (RPL) is associated with severe physical and psychological morbidity, for which there is no treatment options. The pathophysiology involves deficiency in proliferation and migration capacities of endometrial stromal cells (hESCs) impairing embryo implantation and development. Animal venoms are rich sources of bioactive molecules and despite its known toxic effects, they also have protective components such as pro-proliferative molecules, growth factor-like, anti-apoptotic and anti-oxidant. Study design, size, duration This study was an experimental in vitro with endometrial stem cells. Treatment duration was 8–72h. Every assay had control cells exposed to phosphate buffered saline (PBS). Participants/materials, setting, methods hESCs were isolated from fresh human endometrial biopsies and characterized according standard protocols. Then the effects of L. obliqua venomous secretions on cell viability, proliferation and migration were determined using MTT, wound-healing assay, sulforhodamine B (SRB) assay and measuring the immunocontent of Ki67. Venom components involved in cell enhancing effects were also identified by classical chromatographic methods and proteomic analysis. Assays were conducted in triplicate. Main results and the role of chance The hESCs in culture showed adhesiveness properties, presented a fusiform fibroblastoid morphology and ability to in vitro differentiate into adipocytes, osteocytes and chondrocytes. The expression of cell surface markers was also characterized by flow cytometry. hESCs were positive for mesenchymal markers (CD105, CD90 and CD73) and negative for hematopoietic markers (CD45 and CD11), indicating that isolated cells have potential for multilineage differentiation. L. obliqua bristle extract (LOBE) increased dose-dependently hESCs viability in a concentration range varying from 0.001 to 0.1 µg/mL, independently of the cell isolation bath. For some cell isolates (patient ID 1, 3, 4, 6 and 7) it was observed a slightly reduction in hESC viability at highest LOBE concentrations (10 µg/mL). Treatment increased hESC viability in the presence of low concentrations of fetal bovine serum (1% FBS) and even in its complete absence. This effect was long lasting, being significant up to 72 h of incubation with LOBE in serum deprivation conditions. r to identify the potential molecules involved in the cytoprotective action, a mass spectrometry-based proteomic analysis was performed. It was identified a total number of 430 proteins in LOBE and 312 proteins in L. obliqua hemolymph. Limitations, reasons for caution This study was only conducted in vitro. Wider implications of the findings: In this work we reported the identification of at least six protein classes with cytoprotective properties through proteomic analysis and isolated one fraction enriched in this cytoprotective factors. L. obliqua secretions induced increase in hESCs viability, proliferation and migration mainly by the protection against oxidative damage and ERK-dependent pathway activation. Trial registration number Not applicable

Clinical Manifestation and Management of Terrestrial Animal Bites

Background: Terrestrial animal bites wounds are injuries caused by terrestrial animals' mouths and teeth. Aerobic and nonaerobic bacteria cause 30–60% of the secondary bacterial infections due to animal bites. Rabies is an infectious disease and it is the most dangerous viral infection caused by animal bites. Also, venomous animal bites can be fatal and cause death if not treated well. Purpose: To identify the clinical manifestation, first aid, and management of terrestrial animal bites to reduce morbidity and mortality. Review: Wounds and crush injuries caused by animal bites are prone to infection. Aerobic bacteria, such as Pasteurella multocida, Staphylococcus spp. (including methicillin–resistant Staphylococcus aureus (MRSA)), Capnocytophaga canimorsus, and Bartonella henselae, and anaerobic bacteria, such as Porphyromonas spp. are commonly found pathogens in animal bite wounds. Rabies, the most dangerous viral infection, occurs in wounds infected by the rabies virus. The virus enters the nerve tissue, multiplies, and spreads to the central nervous system. This can cause disability, and it is life-threatening. In snakebites, management of basic life support, transportation to the hospital, clinical assessment, and immediate resuscitation are the most important procedures. Conclusion: Animal bite wounds are injuries caused by animals' mouths and teeth. Dogs, cats, and snakes are terrestrial animals that most likely attack humans. Proper diagnosis, first aid, and comprehensive management are needed to reduce morbidity and mortality.

Preclinical Evaluation of Antidotal Property of Mritasanjeevana agada in Poisoning- A Study Protocol

Background: As the poisoning is becoming a threat to rural India, it is necessary to increase the survival time to avail the primary treatment. For the treatment of poisoning, Agada is described in Ayurveda as an antidote. Agada is a polyherbal or herbomineral formulation constituted with combination antitoxic drugs along with some antioxidant, immunomodulator or hepatoprotective drugs. But they need to be revalidated for their efficacy and safety on the basis of contemporary assessment parameters
 Aim: Evaluation of antidotal property of Mritasanjivana Agada in poisoning.
 Objectives:
 
 To increase the survival time after the administration of Mritasanjivana Agada in snake venom and aluminium phosphide poisoning in albino mice.
 To compare the efficacy of Mritasanjivana Agada and Anti-snake venom as an antidote.
 To standardize the Mritasanjivana Agada.
 
 Methodology: Mritasanjeevana Agada will be prepared and standardized. Cobra venom poisoning and aluminium phosphide poisoning have been selected as the representative for the animate poison and artificial/ synthetic poison. After inducing poisoning in mice, one group will receive its standard antidote and other will receive standard antidote with Mritasanjivana Agada. The third group will receive only Mritasanjivana Agada without its standard antidote. All the groups will be assessed on the basis of hematology, biochemistry, Superoxide dismutase (SOD) level, Malondialdehyde (MDA) level and histopathology in case of death of the animals.
 Results: Mritasanjeevana agada is expected to increase the survival time in the treatment of snake venom and aluminium phosphide poisoning in albino mice.
 Conclusion: Mritasanjeevana agada may be as efficacious as Anti-snake venom as an antidote.

Genomic Structure of Two Kv1.3 Channel Blockers from Scorpion Mesobuthus eupeus and Sea Anemone Stichodactyla haddoni and Construction of their Chimeric Peptide as a Novel Blocker.

Different toxins acting on Kv1.3 channel have been isolated from animal venom. MeuKTX toxin from Mesobuthus eupeus phillipsi scorpion and shtx-k toxin from Stichodactyla haddoni sea anemone have been identified as two effective Kv1.3 channel blockers. In this work, we characterized the genomic organization of both toxins. MeuKTX gene contains one intron and two exons, similar to the most scorpion toxins. There are a few reports of genomic structure of sea anemone toxins acting on Kv channels. The sequence encoding mature peptide of shtx-k was located in an exon separated by an intron from the coding exon of the propeptide and signal region. In order to make a peptide with more affinity for Kv1.3 channel and greater stability, the shtx-k/ MeuKTX chimeric peptide was designed and constructed using splicing by overlap extension-PCR (SOE-PCR) method. MeuKTX, shtx-k, and shtx-k/MeuKTX were cloned and the expression of the soluble proteins in E. coli was determined. Molecular docking studies indicated more inhibitory effect of shtx-k/MeuKTX on Kv1.3 channel compared to shtx-k and MeuKTX toxins. Key amino acids binding channel from both toxins, also involved in interaction of chimeric peptide with channel. Our results showed that the fusion peptide, shtx-k/MeuKTX could be an effective agent to target Kv1.3 channel.

Computational Study of Scorpion Venom (Lychas Mucronatus) Activity as Antimicrobial Peptides (AMPs) to the SARS-CoV-2 Main Protease for the Future Coronavirus Disease (COVID-19) Inhibitors

The 2019 coronavirus pandemic disease (COVID-19) is still declared a global pandemic by the World Health Organization (WHO). Therefore, an effort that is considered effective in finding therapeutic agents is needed to prevent the spread of COVID-19 infection. One of the steps that can be chosen is by utilizing antimicrobial peptides (AMPs) from animal venom by targeting the specific receptor of SARS-CoV-2, namely the main protease (Mpro). Through this research, a computational approach will be conducted to predict antiviral activity, including protein-peptide docking using PatchDock algorithm, to identify, evaluate, and explore the affinity and molecular interactions of four types of antimicrobial peptides (AMPs), such as Mucroporin, Mucroporin-M1, Mucroporin-S1, and Mucroporin-S2 derived from scorpion venom (Lychas mucronatus) against main protease (Mpro) SARS-CoV-2. These results were then confirmed using protein-peptide interaction dynamics simulations for 50 ns using Gromacs 2016 to observe the molecular stability to the binding site of SARS-CoV-2 Mpro. Based on protein-peptide docking simulations, it was proven that the Mucroporin S-1 peptides have a good affinity against the active site area of SARS-CoV-2 Mpro, with an ACE score of −779.56 kJ/mol. Interestingly, Mucroporin-S1 was able to maintain the stability of its interactions based on the results of RMSD, RMSF, and MM/PBSA binding free energy calculations. The results of the computational approach predict that the Mucroporin-S1 peptide is expected to be useful for further research in the development of new antiviral-based AMPs for the COVID-19 infectious disease.

Skin and poison glands in toads (Rhinella) and their role in defence and water balance

AbstractToads are considered poisonous animals since they have a passive mode of defence relying on cutaneous poison glands, differently from venomous animals who can inject venom in predators/aggressors or prey. Toads of Rhinella marina group are generally large and have a broad distribution in South America, inhabiting a wide range of environments. In this paper, we studied the toads Rhinella icterica from the Atlantic rainforest, and Rhinella jimi from the Brazilian Semiarid Caatinga, analysing aspects of natural history and comparing their skin morphology, the presence of macroglands, their resistance to water loss and rates of water uptake. In periods of extreme drought, R. jimi uses rock cracks as refuges, exposing only the head and regions of accumulation of poison glands. The skin of R. jimi showed higher number of poison glands with hydrophilic content than R. icterica. R. jimi also had a thicker skin, which can be related to its superior resistance to water loss. It also showed high rates of rehydration in association with a peculiar behaviour using the limbs to spread water onto highly glandular skin areas, suggesting that poison glands may also act in water balance in addition to chemical defence.

Animal Venoms and Their Components: Molecular Mechanisms of Action

Animal venoms comprise numerous toxin families, consisting mainly of peptides and proteins [...].

Variation of Two S3b Residues in KV4.1-4.3 Channels Underlies Their Different Modulations by Spider Toxin κ-LhTx-1.

The naturally occurred peptide toxins from animal venoms are valuable pharmacological tools in exploring the structure-function relationships of ion channels. Herein we have identified the peptide toxin κ-LhTx-1 from the venom of spider Pandercetes sp (the Lichen huntsman spider) as a novel selective antagonist of the KV4 family potassium channels. κ-LhTx-1 is a gating-modifier toxin impeded KV4 channels’ voltage sensor activation, and mutation analysis has confirmed its binding site on channels’ S3b region. Interestingly, κ-LhTx-1 differently modulated the gating of KV4 channels, as revealed by toxin inhibiting KV4.2/4.3 with much more stronger voltage-dependence than that for KV4.1. We proposed that κ-LhTx-1 trapped the voltage sensor of KV4.1 in a much more stable resting state than that for KV4.2/4.3 and further explored the underlying mechanism. Swapping the non-conserved S3b segments between KV4.1(280FVPK283) and KV4.3(275VMTN278) fully reversed their voltage-dependence phenotypes in inhibition by κ-LhTx-1, and intensive mutation analysis has identified P282 in KV4.1, D281 in KV4.2 and N278 in KV4.3 being the key residues. Furthermore, the last two residues in this segment of each KV4 channel (P282/K283 in KV4.1, T280/D281 in KV4.2 and T277/N278 in KV4.3) likely worked synergistically as revealed by our combinatorial mutations analysis. The present study has clarified the molecular basis in KV4 channels for their different modulations by κ-LhTx-1, which have advanced our understanding on KV4 channels’ structure features. Moreover, κ-LhTx-1 might be useful in developing anti-arrhythmic drugs given its high affinity, high selectivity and unique action mode in interacting with the KV4.2/4.3 channels.

Applications of venom biodiversity in agriculture

Agriculture can benefit from the biotechnological use of animal venom biodiversity. We explored the patent database to find the prevailing applications of scorpion, snake, spider, bee, and wasp venoms for agricultural purposes. We searched for patents registered worldwide using the keywords “animal species” AND “venom” associated with the Cooperative Patent Classification (CPC) subclasses, based on Google Patents by November 2020. The results indicate an increasing frequency in patents related to animal venoms. Scorpion, snake, and wasp appeared most frequently, besides other species. The inventors concentrate on two subclasses, namely new plant varieties development (A01H) and biopesticides (A01N). Monsanto and other giant agricultural and biotechnology companies lead the list in the number of patents. New varieties of crops, like soybean, corn, cotton, rice, and wheat, are the most frequent inventions. The benefits of using natural venoms in insect-resistant plant varieties and biopesticides are pertinent to agriculture, the environment, and human health.

Venom-Derived Neurotoxins Targeting Nicotinic Acetylcholine Receptors

Acetylcholine was the first neurotransmitter described. The receptors targeted by acetylcholine are found within organisms spanning different phyla and position themselves as very attractive targets for predation, as well as for defense. Venoms of snakes within the Elapidae family, as well as those of marine snails within the Conus genus, are particularly rich in proteins and peptides that target nicotinic acetylcholine receptors (nAChRs). Such compounds are invaluable tools for research seeking to understand the structure and function of the cholinergic system. Proteins and peptides of venomous origin targeting nAChR demonstrate high affinity and good selectivity. This review aims at providing an overview of the toxins targeting nAChRs found within venoms of different animals, as well as their activities and the structural determinants important for receptor binding.

Global View on Ant Venom Allergy: from Allergenic Components to Clinical Management

Hymenoptera venom allergy is characterised by systemic anaphylactic reactions that occur in response to stings from members of the Hymenoptera order. Stinging by social Hymenoptera such as ants, honeybees, and vespids is one of the 3 major causes of anaphylaxis; along with food and drug exposure, it accounts for up to 43% of anaphylaxis cases and 20% of anaphylaxis-related fatalities. Despite their recognition as being of considerable public health significance, stinging ant venoms are relatively unexplored in comparison to other animal venoms and may be overlooked as a cause of venom allergy. Indeed, the venoms of stinging ants may be the most common cause of anaphylaxis in ant endemic areas. A better understanding of the natural history of venom allergy caused by stinging ants, their venom components, and the management of ant venom allergy is therefore required. This article provides a global view on allergic reactions to the venoms of stinging ants and the contemporary approach to diagnose and manage ant venom allergy.