D'Amélio F, Vigerelli H, de Brandão Prieto da Silva ÁR
… +1 more, Kerkis I
J Venom Res
· 2021 · PMID 34123362
Belonging to the Viperidae family, are widely distributed in South America, tropical savanna ecoregion (Cerrado) of Argentina, Bolivia, Brazil, and Paraguay with medical importance in Brazil. Accidents caused by this sp...Belonging to the Viperidae family, are widely distributed in South America, tropical savanna ecoregion (Cerrado) of Argentina, Bolivia, Brazil, and Paraguay with medical importance in Brazil. Accidents caused by this species have a rapid local action with the development of tissue inflammation, causing erythema, pain, and increased clotting time, which can culminate in gangrene or tissue necrosis. venom has a rich composition that remains underexplored, which is of utmost importance, both for elucidating the envenoming process and the vast library of new bioactive molecules kind of venom can offer. This review aims to analyze which components of the venom have already been characterized towards its structure and biological effect and highlight the pharmacological and biotechnological potential of this venom. Although snake venoms have been studied for their toxic effects for generations, innovative studies address their components as tools for discovering new therapeutic targets and new molecules with pharmacological and biotechnological potential.
Dorooshi G, Javid ZN, Meamar R
… +3 more, Farjzadegan Z, Nasri M, Eizadi-Mood N
J Venom Res
· 2021 · PMID 34123361
Although the predominant treatment for snakebite is the antivenom, other treatments are also considered. We studied the effects of single or multiple-doses of anti-inflammatory drugs on local, systemic and laboratory fin...Although the predominant treatment for snakebite is the antivenom, other treatments are also considered. We studied the effects of single or multiple-doses of anti-inflammatory drugs on local, systemic and laboratory findings of the snakebite victims. In this cross-sectional study, 101 patients (90 male: 89.1%) with snakebite envenomation who were admitted to the Medical Toxicology Center of Khorshid Hospital, Isfahan, Iran, were investigated. One group (35 patients: 34.7%) received a single-dose of anti-inflammatory drugs containing chlorpheniramine (10mg intramuscular injection) with cimetidine (200mg intravenous injection) or ranitidine (50mg intravenous injection) plus hydrocortisone (100mg intravenous injection). The other 55 patients (54.5%) received multiple doses of the same drug combination every 8hr until the symptoms resolved. Local, systemic symptoms and laboratory findings on admission, and during 24hr and 48hr of admission, were recorded. The frequency of the localized signs of inflammation (p=0.03), swelling (p<0.001) and bruising (p<0.001) showed a significant difference between the two treated groups. In addition, the recovery time in the patients who received multiple doses was faster (p<0.001). There was no significant difference in any of the systemic signs, laboratory findings or the outcome between the patients in the various groups during hospitalization. Our data indicate that the administration of multiple doses of anti-inflammatory drugs had a greater effect on reducing local symptoms of snakebite including inflammatory manifestations.
Rajesh RP, Arun R, Selvam MM
… +3 more, Alphonse CRW, Rajasekar M, Franklin JB
J Venom Res
· 2021 · PMID 34123360
is a common social wasp found in continental Southeast Asia. Despite its wide distribution and abundance, hitherto, there are no studies on small or medium molecular weight components of the venom. For the first time, th...is a common social wasp found in continental Southeast Asia. Despite its wide distribution and abundance, hitherto, there are no studies on small or medium molecular weight components of the venom. For the first time, this study has described the amino acid sequences and its post-translation modifications (PTM's) of four wasp-mastoparans (Ps 1524, Ps 1540, Ps 1556 and Ps 1630), three chemotactic peptides (Ps1417, Ps1434 and Ps1474) and one more (Ps1549) lysine rich peptide from the venom of . There were 27 mass traces obtained from the crude natural venom, in which the complete amino acid sequences of 8 peptides were solved. Further, single disulphide bonded peptides uncommon in wasp venoms were identified. The mastoparan peptides were rich in hydrophobic residues. In addition, the peptides Ps1549, Ps1630, Ps1434 and Ps1417 were found to have unusual PTM's of C-terminal amidation. This preliminary study comprehends the untapped compounds present in wasp venom that are equally valuable to widely studied venoms of snakes, spiders and cone snails.
Kishmiryan A, Ghukasyan G, Ghulikyan L
… +4 more, Darbinyan A, Parseghyan L, Voskanyan A, Ayvazyan NM
J Venom Res
· 2021 · PMID 33747434
Here we describe the processing and development of animal-derived monovalent antibody serum against venom by purification and concentration of the immunoglobulins using caprylic acid. We demonstrate that this new viper...Here we describe the processing and development of animal-derived monovalent antibody serum against venom by purification and concentration of the immunoglobulins using caprylic acid. We demonstrate that this new viper venom antiserum is pre-clinically effective in neutralizing lethal toxicity and hemorrhagicity of the venom of the Armenian Levantine viper - a significant public health problem in Armenia and a wide region from south-east parts of Europe to south-west Asia. The developed product shows a high capacity to inhibit metalloproteinases and phospholipase activity of venom included in the study in comparison to current specific antivenoms, and following additional experimental approvals, it will be possible to derive the monovalent antivenom satisfying international standards, which will be much cheaper and accessible compared with the current market rivals.
We document inadequately diagnosed coagulopathy (potential to be life threatening) due to bite. Although its bites are common in the hills of Nepal, associated envenomations have not been documented elaborately. Herein,...We document inadequately diagnosed coagulopathy (potential to be life threatening) due to bite. Although its bites are common in the hills of Nepal, associated envenomations have not been documented elaborately. Herein, we present the clinical and treatment details of a proven bite and areas where it may pose the risk of envenomations (suggesting huge populations in Asia to be vulnerable to its bites). Its envenomation was managed symptomatically with several non-evidence-based interventions. Since no specific pitviper antivenom is available in Nepal yet, managing coagulopathy associated to envenomation is still challenging. This case emphasizes the need of developing the standard protocol for the diagnosis and management of pitviper bites and study of effectiveness of the available pitviper antivenoms until specific pitviper antivenom is available. Further, the demonstrated distribution localities of this species may have implications for snakebite prevention and designing and distribution of the effective antivenoms.
Ticks are unique hematophagous arthropods and possess an astounding array of salivary molecules that ensure their unnoticed and prolonged attachment to the host skin. Furthermore, ticks are very effective vectors of a di...Ticks are unique hematophagous arthropods and possess an astounding array of salivary molecules that ensure their unnoticed and prolonged attachment to the host skin. Furthermore, ticks are very effective vectors of a diverse spectrum of pathogens. In order to feed, tick chelicerae cut the host epidermis and their hypostome penetrates through the layers of the skin. As a result of laceration of the skin and rupturing blood vessels, a pool of blood is formed in the dermis, serving for intermittent blood sucking and secretion of saliva. Cutaneous injury caused by tick mouthparts should normally elicit wound healing, a complex biological process coordinated by interaction among different host cells, numerous signalling pathways and by a variety of soluble factors including growth factors. Growth factors, endogenous signalling proteins involved in various biological events, are key players in all phases of the skin repair process. Maintaining feeding site integrity by overcoming sequential phases of wound healing is particularly important for ixodid ticks and is governed by bioactive molecules in their saliva. Tick saliva is a complex mixture of proteins, peptides, and non-peptide molecules and its composition depends on the feeding phase, tick developmental stage, gender and/or the presence/absence of microbial agents. In addition to already demonstrated anti-haemostatic, anti-cytokine and anti-chemokine activities, anti-growth factors activities were also detected in saliva of some tick species. In consequence of counteracting host defences by ticks, tick-borne pathogens can be transmitted to and disseminated in the host. Elucidation of the complex interplay between ticks - pathogens - host cutaneous immunity could lead to improved vector and pathogens control strategies. Additionally, tick saliva bioactive molecules have a promising therapeutic perspective to cure some human diseases associated with dysregulation of specific cytokines/growth factors and alterations in their signalling pathways.
Barreto YC, Rosa ME, Zanatta AP
… +4 more, Borges BT, Hyslop S, Vinadé LH, Dal Belo CA
J Venom Res
· 2020 · PMID 33209252
Ureases are metalloenzymes that hydrolyze urea to ammonia and carbamate. The main urease isoforms present in the seeds of (jack bean urease - JBU and canatoxin) exert a variety of biological activities. The insecticidal...Ureases are metalloenzymes that hydrolyze urea to ammonia and carbamate. The main urease isoforms present in the seeds of (jack bean urease - JBU and canatoxin) exert a variety of biological activities. The insecticidal activity of JBU is mediated, at least in part, by jaburetox (Jbtx), a recombinant peptide derived from the JBU amino acid sequence. In this article, we review the neurotoxicity of Jbtx in insects. The insecticidal activity of Jbtx has been investigated in a variety of insect orders and species, including Blattodea (the cockroaches , , e ), Bruchidae ( - cowpea weevil), Diptera ( - mosquito), Hemiptera ( - cotton stainer bug; - large milkweed bug, and the kissing bugs and ), Lepidoptera ( - fall army worm) and Orthoptera ( - locust). In , the injection of Jbtx induces marked alteration of locomotor and grooming behavior, whereas in Jbtx causes leg paralysis, an extension of the proboscis and abnormal antennal movements. Electromyographical analysis showed that Jbtx causes complete neuromuscular blockade in . The same treatment in and causes a decrease in the action potential firing rate. Jbtx forms membrane pore-channels compatible with cations in bilipid membranes. A study using voltage-gated sodium (Nav1.1) channels that were heterologously expressed in oocytes correlated the entomotoxicity of Jbtx with the activation of these channels. Taken together, these findings demonstrate the potential of this peptide as a natural pesticide.
Schezaro-Ramos R, Collaço RC, Cogo JC
… +4 more, Dal-Belo CA, Rodrigues-Simioni L, Rocha T, Randazzo-Moura P
J Venom Res
· 2020 · PMID 33024546
produces similar local effects to snakebite, which can induce misidentification and bothropic antivenom administration. Antivenom therapy is effective, but has its limitations regarding local damage. Since plants are us...produces similar local effects to snakebite, which can induce misidentification and bothropic antivenom administration. Antivenom therapy is effective, but has its limitations regarding local damage. Since plants are used in folk medicine to treat snakebite victims, we evaluated the protective properties of and extracts against and venoms. Preparations pretreated with both extracts inhibited > 90% the venom-induced neuromuscular blockade, and 52% to 81% the venom-induced blockade. inhibited the myonecrosis promoted by both venoms; however, prevented only the myofilaments hypercontraction. Regarding haemorrhagic activity, was more effective against venom, while was more effective against venom. On the other hand, for oedema-forming activity the results were the opposite. Considering that both extracts prevented (to different levels) the main manifestations of both snakebites (local symptoms), we endorse further studies involving these plants as coadjuvant in snakebite therapeutics.
Kryukova EV, Vulfius CA, Ziganshin RH
… +4 more, Andreeva TV, Starkov VG, Tsetlin VI, Utkin YN
J Venom Res
· 2020 · PMID 33024544
Venoms of viperid snakes affect mostly hemostasis, while C-type lectin-like proteins (CTLPs), one of the main components of viperid venoms, act as anticoagulants, procoagulants, or agonists/antagonists of platelet activa...Venoms of viperid snakes affect mostly hemostasis, while C-type lectin-like proteins (CTLPs), one of the main components of viperid venoms, act as anticoagulants, procoagulants, or agonists/antagonists of platelet activation. However, we have shown earlier that CTLPs from the saw-scaled viper , called emunarecins EM1 and EM2, were able to inhibit nicotinic acetylcholine receptors (nAChRs) in neurons of a pond snail (). Here we analysed the structure of the emunarecins by mass spectrometry and report that EM1 and EM2 inhibit fluorescent α-bungarotoxin binding to both muscle-type nAChRs from and human neuronal α7 nAChRs. EM1 at 23µM and EM2 at 9µM almost completely prevented fluorecsent α-bungarotoxin binding to muscle-type nAChRs. Interaction with human neuronal α7 nAChR was weaker; EM1 at the concentration of 23µM blocked the α-bungarotoxin binding only by about 40% and EM2 at 9µM by about 20%. The efficiency of the EM2 interaction with nAChRs was comparable to that of a non-conventional toxin, WTX, from cobra venom. Together with the data obtained earlier, these results show that CTLPs may represent new nAChR ligands.
The western diamondback rattlesnake () is a common and widespread North American pit viper species, and its venom possesses medical applications. In this research, we identified 14 of the most common transcripts encoding...The western diamondback rattlesnake () is a common and widespread North American pit viper species, and its venom possesses medical applications. In this research, we identified 14 of the most common transcripts encoding 11 major venom toxins including transcripts for a three-finger toxin (3FTx) from the crude venom of three-dimensional (3D) structures of 9 venom toxins were predicted by using deduced toxin amino acid sequences and a computer programme-MODELLER. The accuracy of all predicted toxin structures was evaluated by five stereochemical structure parameters including discrete optimised protein energy (DOPE) score, root mean square deviation (RMSD), Z-score, overall quality factor (ERRAT), and φ/ψ dihedral angle distribution of toxin backbone Cα residues, resulting that the overall predicted models are satisfied quality evaluation checks. Our present toxin transcripts and simulated individual toxin structures are important not only for revealing species-specific venom gene expression profiles, but also for predicting the toxin-toxin interactions and designing the structure-based toxin inhibitors for the treatment of snakebites.
The secretions of the Giant Monkey Frog are used by populations in the Amazon regions (mainly the indigenous Katukinas and Kaxinawás). The so-called "toad vaccine" or "kambô" is applied as a medication for infections an...The secretions of the Giant Monkey Frog are used by populations in the Amazon regions (mainly the indigenous Katukinas and Kaxinawás). The so-called "toad vaccine" or "kambô" is applied as a medication for infections and to prevent diseases, and also as physical and mental invigorator, and analgesic. Since the 1980s, researchers and companies have been interested in the composition of these secretions. Phyllomedusin, phyllokinin, caerulein and sauvagine are the polypeptides in these secretions that can cause intense effects on smooth muscles, vessels provoking, nausea and vomiting, arterial hypotension, flushing, palpitations, nausea, vomiting, bile secretion and angioedema. These actions are similar to bradykinin. However, the feeling of well-being and improvement of motor skills described by the users seems to be associated with dermorphine, caerulein or deltorphin - peptides with analgesic properties - and their affinity for the opiate receptor systems. Caerulein is a peptide that increases digestive secretions. Phyllomedusin and Phyllokinin lead to blood pressure and digestive effects. Sauvagine release corticotropin and mimics the physiological reactions of exposure to stress. Deltorphins and dermorphins have high affinity for the opiate receptor system and can lead to analgesia. The fame acquired by the therapy motivated the use by individuals from urban areas worldwide, without safety considerations. While in indigenous communities, there is an entire cultural tradition that provides relative safety to the application, however, the extension of use to individuals from urban areas worldwide is a problem, with reports of severe adverse effects and deaths. Undoubtedly, the skin secretions of the genus contain substances of intense pharmacological action and that can lead to research for therapeutic uses, but control over their application in rituals outside the forest is needed due the risks presented.
Phylogenetic evidence is provided for horizontal transfer of a natterin-like toxin encoding gene from fungi into the genome of the coral . Sequencing analysis of the coral tissues supported that a fungal taxon predicted...Phylogenetic evidence is provided for horizontal transfer of a natterin-like toxin encoding gene from fungi into the genome of the coral . Sequencing analysis of the coral tissues supported that a fungal taxon predicted to be the most likely gene donor was represented in the coral microbiome. Further bioinformatics data suggested widespread recruitment of the natterin-like gene into venomous terrestrial invertebrates, and repositioning of this gene to non-toxic functions in non-venomous teleost fish.
Gardiner M, Weldon A, Poindexter SA
… +2 more, Gibson N, Nekaris KAI
J Venom Res
· 2018 · PMID 30090322
Slow lorises () are one of six venomous mammals, and the only known venomous primate. In the wild envenomation occurs mainly during conspecific competition for mates and territory, but may also be used as an application...Slow lorises () are one of six venomous mammals, and the only known venomous primate. In the wild envenomation occurs mainly during conspecific competition for mates and territory, but may also be used as an application against parasites or for predator defense. Envenomation in humans is documented, with the most extreme accounts detailing near-fatal anaphylactic shock. From September 2016 - August 2017, we received questionnaire responses from 80 wild animal practitioners working with . in zoos, rescue centres and in the wild. We identified 54 practitioners who had experience of being bitten or were otherwise affected by slow loris venom, and an additional 26 incomplete entries. No fatalities were reported. Fifteen respondents noted that medical intervention was required, 12 respondents indicated no reaction to being bitten (9 of these indicated they were wearing gloves). Symptoms for those affected included: anaphylactic shock, paraesthesia, haematuria, dyspnoea, extreme pain, infection and general malaise. Impact of slow loris bites ranged from instantaneous to long-persisting complications, and healing time ranged from 1 day to >8 months. Extremities, including hands and arms, were mostly affected from the bites. Six of nine species of slow loris were reported to bite, with being the most common in our sample. We make suggestions regarding the use of these highly threatened yet dangerous primates as unsuitable tourist photo props and zoo animal ambassadors. We discuss the medical complications experienced in relation to protein sensitisation, and bacterial pathogenesis. We recommend future work to ascertain the protein content of slow loris venom to aid in enabling mitigation of risks posed.
Khoury J, Dabbousy R, Sadek R
… +4 more, Antoun S, Hleihel W, Legros C, Fajloun Z
J Venom Res
· 2017 · PMID 29285352
Because snake venoms are complex mixtures of bioactive molecules, snake bites produce a large panel of symptoms which cannot be totally prevented by current antivenoms. Thus investigating plant extracts for antivenomics...Because snake venoms are complex mixtures of bioactive molecules, snake bites produce a large panel of symptoms which cannot be totally prevented by current antivenoms. Thus investigating plant extracts for antivenomics therapy approaches seemed relevant. Here, we evaluated the potency of the aqueous Buds extract of (ABEE) to counteract the main enzymatic activities of venom. We showed that ABEE efficiently counteracts the proteolytic, Phospholipases A2 (PLA2), and L-aminoacid oxidase activities (LAAO) of venom. ABEE was found to inhibit Acetylcholine esterase (AChE) and to exhibit a potent antioxidant activity. In addition, venom displays antibacterial properties against , which were not inhibited by ABEE. We also showed that of venom lacks AChE, either anti-AChE activities. ABEE represents a promising natural source of antivenomics compounds against the deleterious effects of or other Vipera species bites.
Snakebite envenomation is an important global health concern. The current standard treatment approach for snakebite envenomation relies on antibody-based antisera, which are expensive, not universally available, and can...Snakebite envenomation is an important global health concern. The current standard treatment approach for snakebite envenomation relies on antibody-based antisera, which are expensive, not universally available, and can lead to adverse physiological effects. Phage display techniques offer a powerful tool for the selection of phage-expressed peptides, which can bind with high specificity and affinity towards venom components. In this research, the amino acid sequences of Phospholipase A (PLA) from multiple cottonmouth species were analyzed, and a consensus peptide synthesized. Three phage display libraries were panned against this consensus peptide, crosslinked to capillary tubes, followed by a modified surface panning procedure. This high throughput selection method identified four phage clones with anti-PLA activity against Western cottonmouth venom, and the amino acid sequences of the displayed peptides were identified. This is the first report identifying short peptide sequences capable of inhibiting PLA activity of Western cottonmouth venom , using a phage display technique. Additionally, this report utilizes synthetic panning targets, designed using venom proteomic data, to mimic epitope regions. M13 phages displaying circular 7-mer or linear 12-mer peptides with antivenom activity may offer a novel alternative to traditional antibody-based therapy.
Bihar is the state with the third largest number of snakebite deaths per year in India. This prospective, one-year study of 608 snakebites provides the first data from Bihar on determinants of unfavourable outcomes in sn...Bihar is the state with the third largest number of snakebite deaths per year in India. This prospective, one-year study of 608 snakebites provides the first data from Bihar on determinants of unfavourable outcomes in snakebites. Any delay in reaching hospital raised the risk of a snakebite patient for an unfavourable outcome [OR 8.88, CI 2.04-38.8]. Attending a traditional practitioner prior to presenting to the hospital was the only specific, significant delay [OR 3.52, CI 1.26-9.7]. Prevention of unfavourable outcomes occurred by presenting to hospital in less than 1.5 hours [OR 0.23, CI 0.052-1.0]. Motorbike was the best mode of transport [OR 0.37, CI 0.12-1.1]. Other risk factors were patients aged under 15 years [OR 3.79, CI 1.57-9.12] and bites to the upper limb [OR 2.47, CI 1.01-6.04]. Patients who were envenomated had a higher risk of unfavourable outcome, if referred due to antivenom being unavailable [OR 12.2, CI 1.49-100]. To save lives, it is imperative that measures to reduce delays in getting patients to hospital must be included in snakebite management, alongside continued availability of antivenom and assisted ventilation.
Díaz-García A, Ruiz-Fuentes JL, Rodríguez-Sánchez H
… +1 more, Fraga Castro JA
J Venom Res
· 2017 · PMID 29285349
scorpion venom has demonstrated high cytotoxic activity in epithelial cancer cells. In the present study, the effect of scorpion venom on cell viability and apoptosis was evaluated in the MDA-MB-231 human breast carcinom...scorpion venom has demonstrated high cytotoxic activity in epithelial cancer cells. In the present study, the effect of scorpion venom on cell viability and apoptosis was evaluated in the MDA-MB-231 human breast carcinoma cell line. Cell viability was analyzed using MTT assay. The cell death event was examined trough end-point RT-PCR to identify the expression of apoptosis-related genes, fluorescent microscopy and mitochondrial membrane potential (ΔΨm) alteration. The results demonstrated that scorpion venom induced apoptosis in MDA-MB-231 cells in a time-dependent manner. Besides, scorpion venom treatment also resulted in p53, bax, noxa, puma, caspase 3 and p21 over-expression, while the expression of bcl-2 and bcl-xl was down-regulated. Apoptosis was associated with depolarization of ΔΨm. The overall effect indicates that the selective cytotoxic effect of the scorpion venom is associated with its apoptosis-inducing effect through the mitochondrial pathway. Therefore, scorpion venom may be an interesting natural extract for further investigation in breast cancer treatment strategies.
Meléndez-Martínez D, Macías-Rodríguez E, Vázquez-Briones R
… +5 more, López-Vera E, Sandra Cruz-Pérez M, Vargas-Caraveo A, Gatica-Colima A, Fernando Plenge-Tellechea L
J Venom Res
· 2017 · PMID 28540032
The Mexican black-tailed rattlesnake is distributed in the Mexican plateau. Its venom is known to cause hemolysis and presents fibrinogen coagulase, collagenase and fibrinolytic activities. These activities may be assoc...The Mexican black-tailed rattlesnake is distributed in the Mexican plateau. Its venom is known to cause hemolysis and presents fibrinogen coagulase, collagenase and fibrinolytic activities. These activities may be associated with hemostatic alterations, such as platelet aggregation, hemolysis and fibrinolysis, often described in ophidic accidents. However, the mechanisms of action of the venom remain unclear. In this study we investigated the hemotoxic, neurotoxic, and vasculotoxic effects of the venom. We found that this venom produces two types of hemolytic responses, Oxyhemoglobin release and Methemoglobin formation. As a result of the cytotoxicity to endothelial cells produces morphological biphasic toxicity. The first step in this process is characterized by morphological changes, as well as the loss of cellular adhesion and reduction in thickness. The second phase is characterized by massive cellular aggregation and death. It also induced laminin, type IV collagen, perlecan and nidogen degradation. However, the venom did not modulate the muscular fetal and neuronal nicotinic acetylcholine receptors activity. Thus, we concluded that the venom produced hemolysis and hemorrhages via degradation of the basement membrane components and endothelial cell cytotoxicity, but not by neurotoxicity at the receptor level in nicotinic acetylcholine receptors.