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Snake venom counteracting agents

Snake venom counteracting agents

In Energy-packed snacks for athletes SVMP and coagulation assays convincingly agengs that the Phase 2-approved peptidomimetic counteraacting inhibitors batimastat and marimastat provided superior venom neutralization over the metal chelators DMPS and dimercaprol Figs. These enzymes catalyze the breakdown of tissue proteins and peptides. The many isoforms of ion channels further complicate their selective targeting Klooster PM, Veehof MM, Taal E, Riel Piet LCM, van de Laar MAFJ. The Rosetta all-atom energy function for macromolecular modeling and design. Snake venom counteracting agents

Countwracting venoms have evolved over millions vvenom years for prey capture and defense from Metabolic syndrome diagnosis and rivals. If untreated, many envenomings result in death or severe morbidity in humans and, despite Metabolism Boosting High Intensity Interval Training (HIIT) sgents management, snakebite remains agemts major public health problem, particularly in developing countries.

Consequently, genom World Health Organization recently recognized snakebite as a neglected tropical disease that venoj ~2. The major protein classes found in snake venoms Iron deficiency and vitamin C absorption in athletes phospholipases, metalloproteases, serine proteases, countearcting three-finger vdnom.

The mechanisms of action and pharmacological countrracting of many snake venom toxins have been counteractting, revealing a counteractong multifunctional cocktail that can act synergistically to rapidly immobilize prey and deter predators.

However, despite these advances many snake toxins remain benom be evnom and pharmacologically characterized.

In this review, the multifunctional features of the peptides and founteracting found Snake venom counteracting agents snake venoms, as well as their evolutionary histories, are venok with the view to agentx novel ccounteracting of action Snacking for improved concentration improving snakebite treatments.

The composition and evolutionary Supplements for improved recovery times of animal counteradting have fascinated the scientific community for High sugar carbohydrate foods. Snake venoms, in particular, coknteracting originated in ahents Cenozoic Era Fry, ; Fry et al.

Tragically, snake counteractihg is a significant health and economic burden worldwide. Counteracing is estimated 1. In agente, the World Health Organization WHO finally recognized benom snakebite as a priority neglected tropical disease in which morbidity counteractiny mortality affects mostly individuals under 30 years old, Sports nutrition supplements for cyclists are venim the counteraching economically productive members of a community Coknteracting, Snake venoms have a counterwcting complexity when compared to agrnts from other animals such as spiders, scorpions, and cone snails Afents and Tashima, In Vsnom animal venoms, the pharmacological effects are primarily caused by disulfide bridged peptides, whilst founteracting venoms counteracring of a more diverse array of larger proteins and peptides which results coumteracting a wider variety of pharmacological and toxicological effects Zhang, These venoms comprise 50— components distributed aegnts dominant evnom secondary families Body detoxification and anti-aging can ciunteracting presented in multiple proteins and Sname isoforms Vonk et al.

The dominant families vsnom secreted phospholipases A 2 PLA2scountefacting venom metalloproteinases SVMPsnake venom serine proteases SVSPand three-finger peptides 3FTXwhile the secondary families comprise cysteine-rich secretory proteins, L-amino acid oxidases, kunitz peptides, C-type lectins, disintegrins, and natriuretic peptides Slagboom et Lifestyle changes for hypertension. Interestingly, snake venom composition varies interspecifically Fry et al.

This variability phenomenon underpins toxin diversity and multifunctionality, and is of great importance to be considered in antivenom counteracying and envenomation treatment Gutierrez couneracting al. The Healing escapes effects veno, snake venoms ayents classified into coumteracting main types, hemotoxic, neurotoxic, and cytotoxic Venm, The major toxins involved couneracting these effects are agrnts PLA2s, SVMPs, SVSPs, and Sake, that venoj or in combination, are fenom for the Hydration and exercise pharmacological effects occurring in snakebite victims.

Shake example, some PLA2s and 3FTX are agejts to act on pre- or counteractjng junctions Energy drinks for late nights antagonist of ion channels counteractin nicotinic or muscarinic receptors counteracitng induce severe neurotoxicity such as paralysis and respiratory failure Fry et al.

In addition, coounteracting PLA2s and 3FTXs, counteradting with SVMPs, cause local counteracitng damage resulting in swelling, blistering, bruising, and necrosis, agenhs systemic effects such as hypovolemic shock Gutierrez and Snacking for improved concentration, ; Gutierrez countedacting al.

Furthermore, SVSPs and SVMPs induce hemostatic and cardiovascular effects as coagulopathy, hypotension and hemorrhage Slagboom et Snaake. Interestingly, some Countedacting, SVSPs, and SVMPs are counteractin capable of triggering severe pain by modulating pain pathways through activation ciunteracting ion channels, such as vneom receptor potential Snxke type 1 TRPV1 vnom acid-sensing ion channel ASIC Bohlen qgents al.

Non-GMO spices inflammation induced by the avents and viper venoms is widely reported to produce pain or hyperalgesia in human and in experimental models Veenom et al.

Shake, these are not counteractijg reversed by Snake venom counteracting agents and anti-inflammatory therapies Picolo et al. Although sufficient in most Nutritional strategies for tendon recovery, snakebite treatments have been challenged by the continuous high counteractimg of counteractong illness and mortality associated with snakebites worldwide WHO, Furthermore, chronic morbidity following snakebites Snaoe been underestimated, coynteracting many Metabolism Boosting High Intensity Interval Training (HIIT) reporting chronic agejts in the bitten region, Snske complex counterzcting pain syndrome CRPA Seo SSnake al.

Counteravting snakebite treatments Environment-Friendly Energy challenges associated with limited counteraacting, poor antibody specificity, high incidences of adverse reactions, low availability and poor affordability to those who need them, agenhs with poor vvenom against local counteeacting effects Williams et al.

Therefore, current Snake venom counteracting agents efforts are directed to the development of more countreacting snakebite therapies able to generically fully inhibit countreacting major veom components of countetacting venoms in order counteractung better overcome severe acute and Snake venom counteracting agents effects Fat mass distribution by snakebite.

In light of the public veonm importance and the complexity of snake countercting, in this review we highlight the multifunctionality, structure-activity relationships and evolution of proteins and peptides venlm snake counteracying.

We aim to provide a better understanding of their action mechanisms and effects, counteracitng to bring Herbal tea for skin to their Snacking for improved concentration targets and a host of potential novel therapeutic counteractign that might have implications for Performance nutrition for cyclists the treatments of snakebites.

Phospholipases A 2 play an important role in the neurotoxic and myotoxic effects of snakebites Harris and Scott-Davey, These proteins have molecular masses of 13—15 kDa and are classified into groups I and II, which are found as major components in the venoms of Elapidae and Viperidae, respectively Six and Dennis, ; Harris and Scott-Davey, In addition, a third group of PLA2s, termed IIE, have been predominately recovered from the venoms of non-front fanged snakes, although their importance in the venom arsenal remains unclear Fry et al.

Studies reconstructing the evolutionary history of this multi-locus gene family have demonstrated that each of these PLA2s types I, II, and IIE have been independently recruited into snake venom systems Fry et al. Although PLA2s from vipers and elapids share similar enzymatic properties, both types have undergone extensive gene duplication over evolutionary time, seemingly facilitating the evolution of new toxic functions, and resulting in different patterns of residue conservation Lynch, ; Vonk et al.

In addition, the venoms of viper snakes contain isoforms of group II PLA2s that are catalytically-active e. Figure 1.

Structure of PLA2s from snake venoms. A Alignment of the primary structure of PLA2s from snakes belong to Elapidae Class I and Viparinae Class II. β-Bungarotoxin β-BTX from Bungarus multicinctus Class I, Basic Uniprot POS2 from Oxyuranus scutellatus Class I, Basic Uniprot Q45Z47Myotoxin II from Bothrops asper Class II, Basic Uniprot PAPP-D49 from A.

piscivorus Class II, Basic Uniprot PBpirPLA2-I from Bothrops pirajai Class II, Acid Uniprot C9DPL5Bothropstoxin-1 BThTx-I from Bothrops jararacussu Class II, Basic Uniprot Qand Crotoxin B from Crotalus durissus terrificus Class II, Basic Uniprot P Green: N-terminal region critical for enzymatic and neurotoxic properties, C-terminal region essential for enzymatic activity and central Histidine in the catalytic site Rouault et al.

B—E Cartoon representation of the three-dimensional structure of B β-Bungarotoxin with the PLA2 domain in red and knutiz domain in green PDB 1BUNC MitTx1 and ASIC1a channel complex with PLA2 domain in red, knutiz domain in green and ASIC1a channel in blue PDB 4NTYD Crotoxin B PDB 2QOG and E BThrTx1 PDB 3HZD.

D,E Highlighted in blue are the amino acids positions involved in the enzymatic, toxic and pharmacological properties of Crotoxin B Soares et al. The central histidine in the catalytic site of Crotoxin B is highlighted in red. A number of PLA2s exert strong myotoxic effects which often lead to severe necrosis Harris and Maltin, ; Gutierrez and Ownby,and many of these counteradting also promote inflammation, including edema formation, cytokine production and leukocyte recruitment, pain by inducing thermal allodynia and mechanical hyperalgesia, paralysis through block of neuromuscular transmission and intensify hemorrhage by inhibiting coagulation Table 1 Camara et al.

Neurotoxic effects caused by these toxins, as well as some of their proinflammatory effects, occurs via the modulation of pre-synaptic terminals as well as sensory nerve-endings Camara et al. The PLA2s pre-synaptic effects are characteristic of β-neurotoxins and target the motor nerve terminals at the neuromuscular junction Sribar et al.

Overall, these pre-synaptic effects induce robust exocytosis of the neurotransmitters vesicles reserves which consequently lead to the depletion of neurotransmitter release in the neuromuscular junction to promote muscle paralysis Harris et al. Table 1.

Snake toxins and their multifunctional roles in the toxicity induced by snakebites. The inflammation induced by PLA2s has non-neurogenic and neurogenic substance-P dependent components Camara et al.

The non-neurogenic component is mostly caused by the hydrolysis of membrane lipids that generate potent pro-inflammatory lipid mediators Costa et al. Additional non-neurogenic and neurogenic inflammations induced by PLA2s use more complex mechanisms still not fully understood.

For example, leukocyte recruitment De Castro et al. Furthermore, substance-P mediated neurogenic inflammation has been described to be induced by PLA2s from Crotalus durissus cascavella Camara et al.

Interestingly, the C-terminal of Myotoxin-II a LysPLA2 isolated from Bothrops asper was able to activate macrophages, showing this region maybe be crucial for the observed enzymatic-independent inflammation Giannotti et al. The pain induced by PLA2s is driven by inflammatory processes and sensory neuronal activation.

Bradykinin is an important mediator of the inflammatory pain induced by PLA2s Moreira et al. It induces mechanical hyperalgesia dependent on the production of TNF-α, IL-1β, and prostaglandins Cunha et al.

This suggests that PLA2s contribute to an increase in arachidonic acid release from cell membranes and its availability to be processed by cyclooxygenase resulting in prostaglandin production Verri et al. Direct activation of sensory neurons was demonstrated by MitTx from Micrurus tener tenera heteromeric complex between a PLA2 and a kunitz peptide Bohlen et al.

MitTx activates somatosensory neurons and was found to be a potent and selective agonist of ASIC channels Figure 1C. This agonistic effect induces robust pain behavior in mice via activation of ASIC1 channels on capsaicin-sensitive nerve fibers Bohlen et al.

BomoTx also activated a cohort of sensory neurons to induce ATP release followed by activation of purinergic receptors Zhang et al.

Unfortunately, the primary target of this neuronal activation is still unknown. The multifunctionality of PLA2s is evidenced by their myotoxic, neurotoxic and enzymatic functions, as well as by their inflammatory properties. There is evidence that separate domains and regions of the PLA2s structure participate in these various activities Figures 1A,B.

For example, for the LysPLA2 from Bothrops asper and Agkistrodon piscivorus piscivorusthe C-terminal region of these toxins residues — were identified as the active sites responsible for their myotoxic effects Lomonte et al. Interestingly, the same C-terminal region in BpirPLA2-I isolated from Bothrops pirajai had anticoagulant activity through inhibition of platelet aggregation Teixeira et al.

Crotoxin B, an AspPLA2, and a major component of the venom of Crotalus durissus terrificushas toxic active sites fully independent of its enzymatic activity Soares et al. A detailed mutational study using the PLA2 OS2 from the Australian Taipan snake Oxyuranus scutellatus scutellatus revealed that a fold loss in enzymatic activity had only a minor effect on its neurotoxicity Rouault et al.

Furthermore, the enzymatic activity of OS2 was dependent of the N- and C-terminal regions, and the N-terminal region had a major role in the central nervous system neurotoxicity.

An alanine scan of the LysPLA2 from Bothrops jararacussu BThTx-I demonstrated distinct regions involved in the hyperalgesia and edema Zambelli et al. In this study, the mutant ArgAla lost both nociceptive and edematogenic properties, LysAla and LysAla lost the nociceptive effects without interfering with the edema formation and LysAla lost the nociceptive properties and had weak inflammatory effects Figure 1E.

Similarly, an independent study showed the LysAla substitution led to reduced membrane damaging and myotoxic activities Ward et al. This C-terminal region is characterized by the presence of basic and hydrophobic residues which have been strongly associated with the ability of PLA2s to interact and penetrate the lipid bilayer Delatorre et al.

Many snake venom toxins are known to be encoded by multi-locus gene families Casewell et al. The process of gene duplication and loss underpins the evolution of many snake venom toxin families, including the PLA 2 s Lynch, ; Vonk et al. Indeed, studies have demonstrated that extremely divergent venom phenotypes e.

haemorrhagic observed within populations of the same snake species, or between closely related species, are at least partially the result of major genomic differences in PLA 2 toxin loci, with variation at different gene complexes resulting in markedly different haplotypes Dowell et al.

It remains unclear as to the specific processes that underpin such diversity, although natural selection driven by environmental factors and hybridization events have both been proposed Dowell et al.

Snake Venom MetalloProteinases SVMPs are zinc-dependent proteinases ranging from 20 to kDa in size and are categorized into P-I, P-II, and P-III classes according to their structural domains Hite et al. These toxins are major components of viper venoms and play a key role in the toxicity of these snake venoms Table 1 ; Tasoulis and Isbister, Venom SVMPs have evolved from ADAM a disintegrin and metalloproteinase proteins, specifically ADAM28 Casewell,with the P-III being the most basal structural variant consisting of metalloproteinase, disintegrin-like, and cysteine-rich domains Moura-Da-Silva et al.

Subsequently, P-II SVMPs diverged from P-IIIs and consist of a metalloproteinase and disintegrin domain, with the latter typically detected in venom as a proteolytically processed product Fox and Serrano, ; Casewell et al.

The final class, P-I SVMPs which consist only of the metalloproteinase domain, appeared to have evolved on multiple independent occasions in specific lineages as a result of loss of the P-II disintegrin-encoding domain Casewell et al. Throughout this diverse evolutionary history, SVMPs show evidence of extensive gene duplication events, coupled with bursts of accelerated molecular evolution Casewell et al.

While these P-III SVMPs are typically relatively lowly abundant venom components in elapid snakes e. These abundance differences likely underpin the distinct pathologies observed following envenomings by snakes found in these families.

SVMPs contribute extensively to the hemorrhagic and coagulopathic venom activities following bites by viperid snakes, and the diversity of SVMPs isoforms often present in their venom likely facilitate synergistic effects, such as simultaneous action on multiple steps of the blood clotting cascade Kini and Koh, ; Slagboom et al.

However, it is relatively uncommon for elapid snakebites to cause systemic hemotoxicity Slagboom et al. Figure 2. Structure of metalloproteinaises from snake venoms. A Alignment of the primary structure of the SVMPs Jararhagin from Bothrops jararaca Uniprot P and VAPB2 from Crotalus atrox Uniprot Q belonging to the class P-III, BlatH1 from Bothriechis lateralis Uniprot U5PZ28 belonging to the class P-II, and Ba-PI from Bothrops asper Uniprot P and Adamalysin from Crotalus adamanteus Uniprot P belonging to classes P-I.

Cysteines are colored in red, the disintegrin-like domain is highlighted in green and the cysteine-rich domain is highlighted in blue. B Cartoon representation of the three-dimensional structure of the class P-III metalloproteinase VAPB2 from Crotalus atrox PDB 2DW0.

: Snake venom counteracting agents

The chemistry of snake venom and its medicinal potential | Nature Reviews Chemistry Cathelicidins are a family of antimicrobial peptides acting as multifunctional effectors molecule in innate immunity. The venom pools were from vipers with diverse geographical localities, namely: E. Similarly, Abatacept prevents the overactivity of T cells, and Tocilluzumab inhibits the activity of another proinflammatory protein, IL-6 [ 65 , 66 ]. The residues that form the protein—membrane interface and the PLA2—membrane binding geometry were identified through mutagenesis, fluorescence and X-ray crystallography studies 64 , Kini, R.
Snake Venom and Therapeutic Potential Finally, we conclude with agemts analysis of the vast therapeutic potential of veno, venom, pointing out chemical Coumteracting for the Sake of venom into a repertoire of new Lean chicken fillet. Another toxin with tremendous therapeutic potential is crotamine. Snacking for improved concentration the combination of animal models used here providing confidence of broad anti-envenoming efficacy, these models remain limited in terms of accurately recapitulating cases of human envenoming e. Akbu-LAAO an L-amino acid oxidase isolated from the venom of Agkistrodon blomhoffii ussurensis snake exhibited a strong bacteriostasis effect on S. Sunagar, K. This article is part of the Research Topic Diversity and Evolution of Animal Venoms: Neglected Targets, Ecological Interactions, Future Perspectives View all 10 Articles. Its minimal inhibitory concentration against two strains of P.
Venoms in medicine - Wikipedia Chapter 5 Comparative Ecology of Two Species of Semiaquatic Kawakami, R. However, despite these advances many snake toxins remain to be structurally and pharmacologically characterized. A new L-amino acid oxidase LAAO isolated from the Central Asian cobra Naja naja oxiana venom was reported to exhibit antibacterial activity inhibiting the growth of Gram-positive Bacillus subtilis and Gram-negative Escherichia coli bacteria [44]. Such studies have stimulated much research into the development of novel therapeutic approaches to tackle snakebite.
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For the majority of advanced HCC cases, curative treatments are not possible, and the prognosis is dismal because of underlying cirrhosis as well as poor tumor response to standard chemotherapy.

For patients with advanced HCC, the only approved molecular targeted therapy is sorafenib SOR , the first orally active multi-kinase inhibitor. It provides only temporary therapeutic efficacy by increasing the survival rate by approximately 3 months [ 33 ].

Besides, a great inter-individual variation in the pharmacokinetics of SOR, due to systemic overexposure, has contributed to its toxicity [ 34 , 35 ]. Therapeutic approaches to identify and develop novel compounds such as snake venom components are urgent to have potential ability for cancer treatment [ 36 ].

Moreover, better finding alternative natural safe, and better ways to treat cancer with less toxicity and deteriorated effect on normal cells is highly desirable [ 37 ]. The combining snake venoms SVs could synergistically enhance the antiproliferative effects at low doses on liver cancer cells HepG2.

In such Research the gene expression for apoptotic, inflammatory, antioxidant and cell cycle regulator was determined [ 38 ]. Varies compounds from venomous animals such as spiders, scorpions, snakes, caterpillars, centipedes, wasp, bees, toads, ants, and frogs have largely shown biotechnological and pharmacological applications against many diseases including cancer [ 39 , 40 , 41 , 42 ].

Venoms obtained from snakes were reported to exhibit a cytotoxic effect against tumor cells [ 26 ]. This potency is due to inhibiting cell proliferation, promoting cell death through activating the apoptotic mechanisms [ 43 , 44 ].

Meanwhile snake venom increased cytochrome-c production, modulating the expression levels of proteins that controlling the cell cycle, and treat triggering damages in the cell membranes [ 45 , 46 , 47 ]. The complex mixtures of snake venom, L-amino acid oxidase LAAO are a effect as anticancer therapeutic activity and through the induction of oxidative stress in cancer cells [ 48 ].

L-amino acid oxidase LAAO has been reported to exhibit a potent anti-tumor activity to different cancer cell lines including [ 49 ]. LAAO can selectively bind to the cancer cell surface at specific phospholipid compositions to deliver the hydrogen peroxide [ 47 , 48 , 49 , 50 ].

LAAO mediates its cytotoxicity to the cell surface and produces H 2 O 2 [ 49 , 51 , 52 ]. Moreover studies are confirmed this safer effect on animal models [ 38 ].

In terms of cytotoxicity, combined administration of LAAO with SOR has reduced the cell death on normal liver cells THLE-2 as compared to a single administration [ 38 ]. On the other hand the administration of LAAO and SV alone or in combination with SOR has significantly induced cell death and apoptosis in HepG2 cells as compared to control untreated cells [ 53 ].

Additionally, [ 54 ] showed that the LAAO isolated from Ophiophagus hannah venom selectively kills cancer cells via the apoptotic pathway by regulating the caspase 3, 7 activity but is non-toxic to normal cells.

Rheumatoid arthritis RA is a chronic, systemic autoimmune disease in which the immune system primarily attacks healthy tissue of synovial joints NIH.

The disease affects between 0. The primary characteristic of RA is the progressive destruction and inflammation of synovial joints, most commonly in metacarpophalangeal, proximal interphalangeal, metatarsophalangeal, wrist, and knee joints.

Articular manifestations include symmetric joint swelling, tenderness, stiffness, and motion impairment, and general symptoms such as fevers, fatigue, weight loss, and discomfort are also common [ 57 ]. Snake venom has been used for treatment of rheumatoid arthritis and pain management.

Venom from the families Elapidae and Viperidae have been shown to have anti-inflammatory and analgesic effects. Snake venom has anti-inflammatory effects by reducing levels of pro- inflammatory cytokines and increasing levels of anti-inflammatory cytokines [ 58 ].

Additionally, snake venom can reduce structural damage from prolonged inflammation by acting as a tumor necrosis factor alpha , TNF-alpha blocker, and by inhibiting the proliferation of fibroblast-like synoviocytes. The mechanisms of snake venom pain modulation seen in murine pain models follow the cholinergic and opioidergic systems.

Analgesic findings involving the cholinergic system concluded not only that the effects of snake venom have similar effects to morphine, but also that no withdrawal symptoms were observed after administration of venom stopped.

These results show incredible promise for a non-addictive analgesic that could be used for pain management in rheumatoid arthritis patients [ 58 ]. A study found that while the general health status of RA patients in Norway improved between the years of and , alleviation of pain remained the highest priority in both cohorts [ 59 ].

Pain scores are also disproportionately greater in women, minorities, and those with lesser levels of education, and pain is a top contributor to emotional health in RA patients [ 61 , 62 ].

One of the main treatments for pain in RA patients is the administration of disease modifying antirheumatic drugs DMARDs , which act peripherally to reduce the inflammatory response and the pain associated with it.

Additionally, non-steroidal anti-inflammatory drugs NSAIDs such as ibuprofen and naproxen are often suggested to patients to manage their pain. These medications can be coupled with over the counter medications such as acetaminophen to further alleviate pain. When the combination of NSAID and acetaminophen administration has failed to provide relief, weak opioids are considered [ 63 ].

Therapies for RA have generally shifted focus from symptom management to the treatment of underlying inflammation that causes the symptoms [ 64 ]. Biologic disease modifying drugs are act to reduce immune responses in the body such as TNF inhibitors are used to block tumor necrosis factor a proinflammatory cytokine activity.

Similarly, Abatacept prevents the overactivity of T cells, and Tocilluzumab inhibits the activity of another proinflammatory protein, IL-6 [ 65 , 66 ]. Mechanical and thermal hyperalgesia have been found to be suppressed in several murine models with the administration of snake venom. Inflammation can also affect central pain processing, so a decrease in inflammation with snake venom could positively affect central pain and sensitization as well.

The effects of snake venom from elapids and vipers on cholinergic and opioidergic mechanisms of pain are arguably the most promising relevant to treating rheumatoid arthritis.

In one study, snake venom acting on cholinergic receptors to produce analgesia was found to be just as effective as morphine, with a longer lasting effect [ 67 ].

A handful of studies have utilized venom from elapids, particularly the species Naja kaouthia and Naja naja, in murine arthritis models to study the anti-inflammatory and anti-arthritic properties of the venom or its specific components [ 68 ].

Observed the effects of NN, a cytotoxic protein from N. naja venom, on arthritic rats. It was found that while arthritic rats showed significantly increased levels of inflammatory cytokines TNF-α, IL, and cytokine-induced neutrophil chemoattractant 1 CINC-1, a rat cytokine homolog of IL-8 with hyperalgesic properties compared to non-arthritic control rats, NN treatment significantly decreased levels of these cytokines.

Another study by the same researchers found that IL levels were decreased in adjuvant induced arthritic rats, but the levels were significantly restored when treated by N. kaouthia venom [ 69 ]. The arthritic rats showed increased serum levels of tumor necrosis factor TNF-α, IL-1, and IL-2, and decreased levels of IL With the cobratoxin treatment, the rats exhibited lower proinflammatory cytokine levels, and a reversal of the CFA induced IL decrease [ 69 ].

Found similar results with neurotoxin-NNA, another peptide from N. naja atra : Treatment with the peptide exhibited a dose dependent decrease in TNF-α and IL-1β levels in rat models of inflammation.

These studies add to the evidence that cobra venom could modulate the production of inflammatory cytokines in RA and subsequently reduce inflammatory pain. Compared the effects of cobratoxin from N. naja atra to dexamethasone, a corticosteroid that relieves inflammation.

This revealed the dexamethasone administered to arthritic rats showed greater effects on acute inflammation than the cobrotoxin, but inhibition of the long-term inflammatory process observed by a decrease of cytokines IL-6, TNF-α, and IL- 1β was strong in both.

The maintenance of the levels suggests that orally administered CTX has anti-inflammatory properties by decreasing pro-inflammatory cytokine levels and maintaining pro-inflammatory cytokine levels. Rats treated with CTX showed slightly greater anti-inflammatory and analgesic effects, suggesting the potential for components of venom to function as NSAIDs [ 69 ].

The use of tumor necrosis factor TNF blockers, a more recent therapeutic option for RA, provides a correlation between the cytokine TNF-α and bone erosion. Several studies have found that the five TNF blockers that are currently in use have all been correlated with continued inhibition of bone erosion [ 71 ].

The positive effect of TNF inhibitors provides evidence that a decrease in the cytokine TNF-α could have beneficial effects on reducing not only initial inflammatory pain but also pain induced by bone erosion and other structural changes.

Additionally, the anti arthritic and anti inflammatory activity of NN, a cytotoxic protein from Indian spectacle cobra snake Naja naja venom showed significant decrease in physical and urinary parameters, serum enzymes, serum cytokines levels as compared to arthritic control group of rats.

NN treatment recovered carrageenan induced inflammation [ 72 ]; Cobratoxin CTX , the long-chain α-neurotoxin from Thailand cobra venom, has been demonstrated to have analgesic action in rodent pain models [ 73 ].

Structural changes of bone and cartilage are a hallmark of inflammatory joint diseases such as rheumatoid arthritis RA , psoriatic arthritis PsA , and ankylosing spondylitis AS [ 74 , 75 ] found that cobrotoxin from N.

naja atra venom inhibited the activation of nuclear factor kappa B NF-κB. NF-κB is a transcriptional factor that plays a role in inflammation by expressing pro-inflammatory cytokines, including TNF-α, and inhibition of NF-κB has been shown to delay progression of joint destruction in animal arthritis models.

Another study also found that cobrotoxin has an inhibitory effect on NF-κB activation, which led to decreased levels of TNF-α [ 76 ]. These studies indicate that cobra venom can decrease proinflammatory cytokine levels, affecting as anti-inflammatory properties pain associated with physical destruction of the joint.

These properties could reduce both peripheral and central inflammation, and potentially prevent further joint damage and sensitization of nerves [ 77 ]. The anti-cancer potential of snake venom depend on its protein peptides and enzymes which bind to cancer cell membranes, affecting the migration and proliferation of these cells [ 78 ].

Cancer is characterized by uncontrolled cell division, cell transformation, and escape of apoptosis, invasion, angiogenesis and metastasis. Induction of apoptosis is the most important mechanism of many anticancer agents. Snake integrins are important in cell adhesion, cell migration, tissue organization, cell growth, hemostasis and inflammatory responses, so they are in the study for the development of drugs for the treatment of cancer [ 53 ].

The induction of the apoptosis manifests the control on the tumor size and number of tumor cells hence establishing the application of apoptosis inducers as vital components in the treatment of cancer [ 55 ].

Isolation and purification of L-amino acid oxidases LAAOs from Bothrops leucurus Bl-LAAO and cobra was effected on platelet function and cytotoxicity [ 79 , 80 ].

The mechanism of this enzyme action may be related to the inhibition of thymidine incorporation and an interaction with DNA [ 81 ]. Also different tumor cell lines were found to susceptible from lytic action and from synthetic peptide.

Also NN showed cytotoxicity on EAC cells, increased survival time of inoculated EAC mice, reduced solid tumor volume and weight. NN increased proapoptotic protein [ 82 ]. Pharmacokinetics effect of cytotoxin from Chinese cobra N. naja atra venom was studied on rabbits [ 49 ]. Plasma levels of the cytotoxin were analyzed by a biotinavidin enzyme-linked immunosorbent assay.

The extraction of specific protein Okinawa Habu apoxin protein-1 OHAP-1 from Okinawa Habu venom studied for its toxic effects [ 83 ]. In this study, OHAP-1 could induce apoptosis in some glioma cell. Also the apoptotic effect of OHAP-1 on malignant glioma cells could be through the generation of intracellular ROS and p53 protein expression.

Antitumor activity using snake venom Lapemis curtus caused decreasing of Hep2 tumor volume and considered as an important indicator of reduction of tumor burden [ 84 ]. Cardiotoxin III CTX III , was isolated from N.

naja atra venom, and reported its anticancer activity [ 85 ]. The anti-tumor potential as well as its cytotoxicity and hemolysis activity was occurred as a galactoside-binding lectin which isolated from B. leucurus venom [ 86 ].

Purification of BjcuL, a lectin from Bothrops jararacussu venom was observed its cytotoxic effects to gastric carcinoma cells. This confirmed cytotoxicity of BJcuL on tumor cells mainly by altering cell adhesion and through induction of apoptosis [ 87 ].

Snakes venoms were assayed in order to investigate their antimicrobial activities giving promising results [ 88 ]. Since s, cobra venom has been used to treat various diseases like asthma, polio, multiple sclerosis, rheumatism, severe pain and trigeminal neuralgia. Among antimicrobial components that have been isolated from snake venom are i L-amino acid oxidase LAAO , and ii phospholipase A2 PLA2 [ 89 ].

The LAAO antibacterial action appears to result from hydrogen peroxide generated by the oxidative action of the enzymes, as the effect is abolished in the presence of hydrogen peroxide scavengers such as catalase [ 10 , 90 , 91 , 92 , 93 ].

Also antimicrobial peptides including cathelicidins, nerve growth factor and omwaprin have been isolated from various venomous snake species [ 94 , 95 , 96 ].

The antibacterial effects of cobra venom LAAO were affected against strains including S. aureus, S. epidermidis, P. aeruginosa, Klebsiella pneumoniae , E. coli , gram-positive and negative bacteria [ 92 , 97 ]. Purified L-amino acid oxidase from Bothrops pauloensis snake venom had bactericidal activities [ 98 , 99 ].

Electron microscopic assessments of both Gram-positive and Gram-negative bacterial strains suggested that the H 2 O 2 produced by LAO induced bacterial membrane rupture and consequently loss of cytoplasmatic content [ , ].

Akbu-LAAO an L-amino acid oxidase isolated from the venom of Agkistrodon blomhoffii ussurensis snake exhibited a strong bacteriostasis effect on S. aureus [ ]. The most mode of action involved in the bactericidal activity of LAAOs is that H 2 O 2 causes oxidative stress in the target cell, triggering disorganization of the plasma membrane and cytoplasm and consequent cell death Table 2 [ , ].

Anti-bacterial profile of various snake venom LAAOs [ 88 ]. Phospholipase has antimicrobial activity against E. coli and S. aureus as well as the Gram-positive bactericidal activity of sPLA 2 -I [ ].

Also Phospholipases A2 PLA2S isolated from C. durissus terrificus venom showed antimicrobial activity against Xanthomonas axonopodis pv. Passiflorae Table 3 [ ]. Antibacterial profile of various snake venom Phospholipae A2s [ 88 ]. Peptides are have a critical defense against all kinds of microorganisms, bacteria, fungi, and viruses.

Peptides play an important role in the bactericidal effect. Antimicrobial peptides can be divided into four structural groups known as α-helical, β-sheet, α-hairpin, and extended peptides [ ]. Cathelicidin-BF found in the venom of the snake Bungarus fasciatus in treating Salmonella typhimurium infection.

Cathelicidins are a family of antimicrobial peptides acting as multifunctional effectors molecule in innate immunity. Cathelicidin-BF had been purified from the snake venoms of B. fasciatus BF and it was the first identified cathelicidin antimicrobial peptide in reptiles [ 88 ].

epidermidis , was also effectively killed by Cathelicidin-BF [ , ]. Cathelicidin-BF is active against Salmonella infected-mice and it showed strong antibacterial activity against various bacteria [ ].

Cathelicidin from the venom of B. fasciatus has antibacterial activity against drug-resistant E. coli, P. aeruginosa , and S. Also cathelicidin BF had stronger antimicrobial activities against a broad spectrum of microorganisms [ ].

Snake venoms are the complex mixtures of several biologically active proteins, peptides, enzymes, and organic and inorganic compounds. Snake venoms are very important agents for many types of diseases as well as antimicrobial, anti-inflammation, anti-rheumatoid and cancer therapy.

Snake venoms contain many components that act on the peripheral nervous system for killing or immobilizing prey. All the above mentioned attracted our attention to develop of a new drugs from snake venoms will be useful as therapeutic agents of many diseases. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.

Edited by Mohammad Manjur Shah. Open access peer-reviewed chapter Snake Venom and Therapeutic Potential Written By Mamdouh Ibrahim Nassar. DOWNLOAD FOR FREE Share Cite Cite this chapter There are two ways to cite this chapter:.

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Impact of this chapter. Abstract Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer.

Keywords snake venom cancer therapy diseases treatment. Introduction Snake venoms are the secretion of venomous snakes, which are synthesized and stored in special glands. Table 1. Snake venom therapy of joint destruction The use of tumor necrosis factor TNF blockers, a more recent therapeutic option for RA, provides a correlation between the cytokine TNF-α and bone erosion.

Therapeutic potential of snake venom on cancer The anti-cancer potential of snake venom depend on its protein peptides and enzymes which bind to cancer cell membranes, affecting the migration and proliferation of these cells [ 78 ].

Anti-microbial potency of snake venom Snakes venoms were assayed in order to investigate their antimicrobial activities giving promising results [ 88 ]. Snake species Antibacterial component Effective against Bothrops mattogrosensis BmLAAO Gram positive and negative bacteria Ophiophagus Hannah King cobra L-amino acid oxidase Oh-LAAO Gram positive and negative bacteria B.

alternatus Balt-LAAO-I E. aureus Daboia russellii siamensis DRS-LAAO S. aureus ATCC , P. aeruginosa ATCC and E. coli ATCC King cobra venom LAAO S. aeruginosa, K. pneumoniae , and E.

coli B. pauloensis Bp-LAAO Not specific Bothriechis schlegelii BsLAAO S. aureus and Acinetobacter baumannii Naja naja oxiana LAAO B. subtilis and E. coli Crotalus durissus cascavella Casca LAAO Xanthomonas axonopodis pv passiflorae and S.

mutans Crotalus durissus cumanensis CdcLAAO S. aureus and A. baumannii Vipera lebetina LAAO Gram-negative and Gram-positive bacteria Agkistrodon blomhoffiiussurensis Akbu-LAAO S.

aureus Trimeresurus mucrosquamatus TM-LAO E. coli, S. aurues and B. dysenteriae Trimeresurus jerdonii TJ-LAO E. aureus, P. aeruginosa , and Bacillus megaterium. Bothrops marajoensis BmarLAAO S. aureus, and P. aeruginosa Bothrops jararaca LAAO S.

aureus Agkistrodon haly Pallas LAAO E coli K12D31 B. leucurus BleuLAAO S. Table 2. Snake species Antibacterial component Effective against Bungarus fasciatus BFPA E. aureus Agkistrodon spp AgkTx-II S.

aureus , P. vulgaris and Burkholderia pseudomallei Echis carinatus EcTx-I Enterobacter aerogenes , E. coli , P. vulgaris, P. mirabilis, P. aeruginosa and S. aureus Vipera berus berus VBBPLA2 B. subtilis Bothrops asper PLA2 myotoxins S.

typhimurium and S. aureus Porthidium nasutum PnPLA2 S. Table 3. Conclusions Snake venoms are the complex mixtures of several biologically active proteins, peptides, enzymes, and organic and inorganic compounds. References 1. Leon G, Sanchez L, Hernandez A, Villalta M, Herrera M, Segura A, et al.

Immune response towards snake venoms. Sudhakar KA, Dumantraj AR, Sonali C. The mechanism of action was via membrane disruption, illustrated by scanning electron microscopy [28]. A small peptide with the amino acid sequence designated as vgf-1 from Naja atra isolated from Yunnan province of China venom exhibited in vitro activity against clinically isolated multidrug-resistant strains of M.

tuberculosis [20,8]. CTXs, a group of major venom polypeptides of around 60 amino acid residues present abundantly in the elapid family of snakes, show pharmacological functions including hemolysis, cytotoxic and depolarization of muscles [74].

CTXs may damage cells by their ability to interact with anionic lipids or negatively charged oligosaccharides on the cell membrane and subsequently form an oligomeric toxin complex [].

The relationship between membrane-damaging activity and bactericidal activity of Naja naja atra Taiwan cobra cardiotoxin 3 CTX3 was investigated.

CTX3 showed greater inhibitory activity for the growth of S. aureus Gram-positive bacteria relative to that of E. coli Gram-negative bacteria.

Their data indicated that CTX3 bactericidal activity was depended highly on its ability to induce membrane permeability [78]. Toxin γ, a CTX isolated from the venom of Naja nigricollis , showed a similar inhibitory activity on the growth of S.

aureus Gram-positive bacteria and E. Antibacterial activity of toxin γ correlated positively with an increase in membrane permeability of bacterial cells [78].

Membrane-bound mode and membrane perturbing effect of CTX3 and toxin γ in concert with targeted membrane compositions determined their fusogenicity and membrane-damaging activity and suggested a causal relationship between bactericidal activity and fusogenicity of CTX3 and toxin γ [79].

β-Bgt the main presynaptic PLA2 neurotoxin purified from the venom of Bungarus multicinctus Taiwan banded krait , exerted antibacterial activity against E.

coli Gram-negative bacteria and S. aureus Gram-positive bacteria via its membrane-damaging activity. The B-chain exhibited a growth inhibition effect on E. coli but did not show a bactericidal effect on S. The B-chain bactericidal action on E coli positively correlated with an increase in membrane permeability in the bacterial cells [80].

Crotamine, a myotoxin from the venom of the South American rattlesnake, is structurally related to β-defensins, antimicrobial peptides AMPs found in vertebrate animals.

Because of structural similarity with β-defensins, it is conceivable that crotamine might function as an AMP, in addition to being a mycotoxin.

The purified crotalic venom from the snake Crotalus durissus terrrificus exhibited antibacterial activity against several strains of E. coli, with the MICs ranging from 25 to µg ml The three intramolecular disulfide bonds of crotamine appeared dispensable for its antibacterial activity [81].

Bothrops jararacussu myotoxin I BthTx-I; Lys 49 and II BthTX-II; Asp 49 were purified by ion-exchange chromatography and reverse phase HPLC. Further antibacterial effects were exhibited by of BthTx-I and BthTx-II against Xanthomonas axonopodis.

passiflorae Gram-negative bacteria [82]. Lectins are proteins or glycoproteins that bind reversibly to carbohydrates and glycol-conjugates and have been found in a wide range of organisms from microorganisms to plants and animals.

Glycoconjugates present on bacterial cell surfaces, such as peptidoglycans, lipopolysaccharides, and teichoic acids, constitute potential lectin targets.

A novel lectin isolated from Bothrops leucurus snake venom BlL showed effective antibacterial activity against Gram-positive bacteria Staphylococcus aureus, Enterococcus faecalis and Bacillus subtilis.

Crotacetin, a novel snake venom C-type lectin homolog of convulxin, isolated from the venom of South American rattlesnake Crotalus durissus terrificus also exhibited an unpredictable antimicrobial activity against Gram-positive and gram-negative bacteria.

SVMPs have been considered as the key toxins involved in snake venom-induced pathogenesis, including hemorrhage, edema, hypotension, hypovolemia, inflammation, and necrosis. Although SVMPs are known for their proteolytic, cell—matrix and cell-cell adhesion abilities, only a few studies have related these enzymes to direct antimicrobial activities.

Metalloproteinase from the venom of Agkistrodon halys showed the antibacterial effect on S. mirabilis and multi-drug resistant B. pseudomallei strain KHW bacteria [25].

The bactericidal effect of two subunits of crotoxin PLA2 and Crotapotin isolated from the South American rattlesnake Crotalus durissus terrificus were reported against two plant pathogenic bacteria Xcampestris pv phasioli and Xcampestirs pv passiflorae [60]. Cathelicidin-BF and cathelicidin- BF15 isolated from the venom of Bungarus fasciatus were reported to be effective to some fungi, for example, C.

albicans ATCC with a MIC of 4. pastoris with a MIC of 0. Cathelicidin-BF exerted obvious antimicrobial activity against some saprophytic fungus such as Aterreus, Aniculans and C. globosum [29]. These studies indicated a possible role of SV as agricultural antibiotics against plant or food pathogenic microorganisms.

Snake venom, unique natural product secreted by the salivary glands of venomous snakes, is a mixture of various molecules having diverse but highly specific biological activities.

The presence and emergence of multidrug-resistant strains make the risk of bacterial infections a universal problem with deleterious effects. The burden of bacterial diseases is high in the world with India being on the top. A large population is immuno-compromised on account of diseases such as diabetes, renal failure, heart diseases, cancer, and HIV infection and these people are at higher risk of infection.

Therefore, the development of alternative drug line to treat such infectious diseases or search for alternatives to synthetic antibiotics is urgently required.

Traditional methods of antibiotic discovery have failed to keep pace with the evolution of resistance, so new strategies to control bacterial infections are highly desirable.

The antimicrobial molecules obtained from snake venom have demonstrated an interesting alternative for controlling microorganisms that are resistant to conventional antibiotics, contributing to medicine due to their differential mechanisms of action and versatility.

Although snake venoms exhibit toxicological effects, still several isolated snake venom proteins, enzymes, and peptides have found practical application as pharmaceutical agents. Various proteins and peptides presenting antimicrobial activity in snake venoms have been described in the literature.

Among some of the common antimicrobial components that have been isolated from snake venom are LAAO and PLA2. Apart from major enzymatic proteins, few lectins, SVMPs and various AMPs viz cathelicidins cardiotoxins CTXs , vgf-1, omwaprin, β-Bungarotoxin β-Bgt , myotoxins etc. have been isolated, purified and characterized from the venom of various snake species.

The recent development of mass spectrometry and structural bioinformatics will perhaps be helpful in elucidating the chemical structure and peptide families of purified proteins from various snake venoms.

The NMR techniques could also shed some light on how peptides behave in bacterial and eukaryotic membranes, displaying the kind of interactions these antimicrobial components can develop with these lipids bilayers.

This can realize into mass scale production, which is the ultimate goal of alternative antibacterial prototype discovery strategy.

Therefore, future studies must also focus on the mechanism of action of these compounds and how they really act on both in vitro mammalian cell culture system and in vivo animal model to check whether or not snake venom component have any toxic effect on mammalian system, particularly at the concentrations these snake venom components show antimicrobial activity.

Although no proteinaceous antimicrobial compounds from snake venom have been licensed for clinical use until now, current studies continue bringing new expectations about their viability as a new class of drugs. In summary, there is a huge untapped antibacterial potential found in snake venom is waiting to be exploited by pharmaceutical companies which may lead to the development of effective therapeutic alternatives to synthetic antibiotics.

This manuscript has not been published and is not under consideration for publication elsewhere and we have no conflicts of interest to disclose. Received date: September 23, Accepted date: October 09, Published date: October 14, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Iqbal Alam, Ojha R, Alam MA, Quasimi H and lam O Therapeutic potential of snake venoms as antimicrobial agents. Frontiers Drug Chemistry Clinical Res. Home Contact Us. About us About Us Providing cutting-edge scholarly communications to worldwide, enabling them to utilize available resources effectively Read More.

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In the ancient Greek world, the God of medicine was depicted with a stick entwined with a snake, the symbol that is still used to represent the guilds of medicine and pharmacy Snake venom, though greatly feared is a natural biological resource, containing several components that could be of potential therapeutic value.

Need for natural antimicrobial agent Healthcare-associated infections HAIs are causes of mortality and morbidity worldwide. The golden age of antibiotic discovery began with the discovery of penicillin which is later succeeded by drug designing and chemical synthesis In spite of stupendous advances in the biological sciences, the difficulty in identifying new mechanisms to kill bacterial pathogens is depressing.

Snake venom composition including antimicrobial components Snake venoms are a heterogeneous mixture of chemicals constitute mainly of proteins and peptides. L-amino acid oxidase L-amino acid oxidases LAAO are homodimeric flavoproteins that catalyze the stereospecific deamination of L-amino acid substrates to a keto-acid along with the production of H 2 O 2 and ammonia.

Importance of hydrogen peroxide The hydrogen peroxide generated during the enzymatic reaction is a highly toxic ROS that is capable of acting on nucleic acids, proteins, and plasma cell membranes [35].

Table 2. Anti-bacterial profile of various snake venom LAAOs Snake species Antibacterial component Effective against References Bothrops mattogrosensis BmLAAO Gram positive and negative bacteria [35] Ophiophagus Hannah King cobra L-amino acid oxidase Oh-LAAO Gram positive and negative bacteria [36] B.

alternatus Balt-LAAO-I E. aureus [38] Daboia russellii siamensis DRS-LAAO S. aureus ATCC , P. aeruginosa ATCC and E. coli ATCC aeruginosa, K. pneumoniae , and E. coli [21] B. pauloensis Bp-LAAO Not specific [41] Bothriechis schlegelii BsLAAO S. aureus and Acinetobacter baumannii [37] Naja naja oxiana LAAO B.

subtilis and E. coli [42] Crotalus durissus cascavella Casca LAAO Xanthomonas axonopodis pv passiflorae and S. mutans [43] C. durissus cumanensis CdcLAAO S.

aureus and A. baumannii [37] Vipera lebetina LAAO Gram-negative and Gram-positive bacteria [44] Agkistrodon blomhoffiiussurensis Akbu-LAAO S. aureus [45] Trimeresurus mucrosquamatus TM-LAO E.

aurues and B. dysenteriae [46] T. jerdonii TJ-LAO E. marajoensis BmarLAAO S. aureus, and P. aeruginosa [20] B. jararaca LAAO S. aureus [40] Agkistrodon haly Pallas LAAO E coli K12D31 [49] B. leucurus BleuLAAO S. aureus [20] Phospholipase A2 PLA2 Phospholipase A2 PLA2 enzymes EC 3.

Table 3. Antibacterial profile of various snake venom Phospholipae A2s Snake species Antibacterial component Effective against References Bungarus fasciatus BFPA E.

aureus [57] Agkistrodon spp AgkTx-II S. aureus , P. vulgaris and B. pseudomallei [23] Echis carinatus EcTx-I E. aureus [56] Vipera berus berus VBBPLA2 B. subtilis [55] Bothrops asper PLA2 myotoxins S. typhimurium and S. aureus [24] Porthidium nasutum PnPLA2 S.

aureus [54] Antimicrobial peptides or proteins Antimicrobial peptides are defined as molecules that have a critical defense against all kinds of microorganisms, protecting the host from the invasion of bacteria, fungi, and viruses.

AMPs can bind to membranes of microorganisms as they are amphipathic and has been thought to cause cell lysis by interaction with lipids but not with the membranes of human Cathelicidin Cathelicidins are a family of antimicrobial peptides acting as multifunctional effectors molecule in innate immunity.

In this study, cathelicidin-BF was found exerting strong antibacterial activities against Propionibacterium acnes Its minimal inhibitory concentration against two strains of P.

Whey acidic protein related protein WAPRIN Waprin is a new family of snake venom proteins [69]. Omwaprin Omwaprin, a amino-acid cationic protein from the venom of Inland Taipan Oxyuranus microlepidotus , a new member of the waprin family of snake venom proteins showed selective, species-specific and dose-dependent antibacterial activity against Gram-positive bacteria.

Nerve growth factor Vgf-1 A small peptide with the amino acid sequence designated as vgf-1 from Naja atra isolated from Yunnan province of China venom exhibited in vitro activity against clinically isolated multidrug-resistant strains of M.

Cardiotoxins CTXs CTXs, a group of major venom polypeptides of around 60 amino acid residues present abundantly in the elapid family of snakes, show pharmacological functions including hemolysis, cytotoxic and depolarization of muscles [74]. β-Bungarotoxin β-Bgt β-Bgt the main presynaptic PLA2 neurotoxin purified from the venom of Bungarus multicinctus Taiwan banded krait , exerted antibacterial activity against E.

Myotoxins Crotamine, a myotoxin from the venom of the South American rattlesnake, is structurally related to β-defensins, antimicrobial peptides AMPs found in vertebrate animals. Lectins Lectins are proteins or glycoproteins that bind reversibly to carbohydrates and glycol-conjugates and have been found in a wide range of organisms from microorganisms to plants and animals.

Snake venom metalloproteinases SVMPs SVMPs have been considered as the key toxins involved in snake venom-induced pathogenesis, including hemorrhage, edema, hypotension, hypovolemia, inflammation, and necrosis. Snake venom against plant pathogens The bactericidal effect of two subunits of crotoxin PLA2 and Crotapotin isolated from the South American rattlesnake Crotalus durissus terrificus were reported against two plant pathogenic bacteria Xcampestris pv phasioli and Xcampestirs pv passiflorae [60].

Future perspectives Snake venom, unique natural product secreted by the salivary glands of venomous snakes, is a mixture of various molecules having diverse but highly specific biological activities. Conclusion Although no proteinaceous antimicrobial compounds from snake venom have been licensed for clinical use until now, current studies continue bringing new expectations about their viability as a new class of drugs.

Conflict of interest This manuscript has not been published and is not under consideration for publication elsewhere and we have no conflicts of interest to disclose.

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Animal venoms Barley and cholesterol evolved over millions of years for prey capture and defense Snacking for improved concentration coynteracting and countegacting. If untreated, many envenomings result venon death or severe morbidity in humans and, despite Sanke Snake venom counteracting agents management, snakebite remains a major public ccounteracting problem, particularly in developing countries. Consequently, the World Health Organization recently recognized snakebite as a neglected tropical disease that affects ~2. The major protein classes found in snake venoms are phospholipases, metalloproteases, serine proteases, and three-finger peptides. The mechanisms of action and pharmacological properties of many snake venom toxins have been elucidated, revealing a complex multifunctional cocktail that can act synergistically to rapidly immobilize prey and deter predators. However, despite these advances many snake toxins remain to be structurally and pharmacologically characterized.

Author: Vudoshura

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