Toxins
Among hundreds, even thousands of proteins found in the venom, there are toxins, as well as nontoxic proteins (which also have pharmacological properties), and many enzymes. High catalytic efficiency, thermal stability and resistance to proteolysis make venom components attractive models to investigate. The venom has been used in the treatment of a variety of patho-physiological conditions in Ayurveda, homeopathy and folk medicine for Centuries. Snake venom toxins affect major systems, like the central nervous system (CNS), cardiovascular system, muscular and vascular systems. With the advent of biotechnology, the efficacy of such treatments has been substantiated by purifying venom components and delineating their therapeutic properties. Various neurotoxicerapeutic properties. Various neurotoxic, cytotoxic or other compounds separated from snake venom are currently used as therapeutic agents like;
- Neurotoxic compounds can be modified to be used as a vector for drug delivery (crossing blood-brain barrier). Neurotoxins affect the nervous system, leading to everything from seizures to death. They can be presynaptic or postsynaptic in action.
- Cytotoxic compounds function as anti-tumor agent
- Some proteins like L-amino acid oxidase can be used as anti-microbial agent
- Cardiotoxic compounds like three-finger toxins can be used for controlling high blood pressure
- Summary table:
| Venom Components | Types of toxin | Toxin activity | Functions (Target/Action) | Family/ Species | References (PMID, Others) |
|---|---|---|---|---|---|
| Acetylcholinesterase | Neurotoxin | Anticancer | Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions | Torpedo californica | 3753747 |
| Alpha-elapitoxin-Nk2a | Neurotoxin | Anticancer | The monomeric form binds with high affinity to muscular and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (nAChR). Causes paralysis by preventing acetylcholine binding to the nAChR. In mice lung cancer, causes reduction of tumor growth | Naja kaouthia | 18381281 |
| C-type lectin (Calcium-dependent lectin) | Neurotoxin | Anticancer | Shows high hemagglutinating activity. In mice model it caused edema and increased vascular permeability. An effective inhibitor of cell growth in renal and pancreatic cancer cell lines, human breast and ovarian carcinoma, glioblastoma | Bothrops jararacussu | 16309723, 10628348, 11478954 |
| Acidic phospholipaseA2 | Neurotoxin, Cytotoxin, Hemotytic | Anticancer, Anti-coagulant | Anticoagulant activities, hemolytic and cytotoxic activities. Inhibits cell migration in human skin melanoma cells and reduces tumor lung colonization of melanoma cells in BALB/c mice | Daboia ruselli siamensis | 22091349 |
| Cytotoxin drCT1 (Three-finger cytotoxin) | Neurotoxin, Cytotoxin, Cardiotoxin, Myotoxin | Anticancer, Anti-proliferative | It has antiproliferative, cytotoxic and apoptotic activities. This protein possess anticancer potential. Also it shows neurotoxicity, cardiotoxicity and myotoxicity | Daboia russelii ruselli | 17055549, 16511326 |
| PhospholipaseA2 | Neurotoxin | Antitumor | PLA2 has a weak enzymatic activity. Inhibits neuromuscular transmission by blocking acetylcholine release from the nerve termini. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides | Naja nigricollis, Bungarus fasciatus, Ophiophagus Hannah | 17166178, 6784277, 2089739, 700923, 9028866, 12217659 |
| L-Aminoacid oxidases (LAAO) | Cytotoxic, Apoptotic | Antitumor | Cytotoxicity in stomach cancer, murine melanoma, fibrosarcoma, colorectal and ovary cell lines. It induces apoptosis in human cervical cancer | Ophiophagus hanna, Agkistrodon halys, Crotalus atrox, Eristicophis macmahoni, Bothrops moojeni, Trimeresurus stejnnegeri, Trimresurus flavoviridis, Agkistrodon halys pallas, Vipera berus berus, Agkistrodo nacutus, Bothrops leucurus | 24683541, 9304806, 8694800, 10727211, 11368308, 16026810, 12963032, 12650671, 19264509, 16574513, 18415865, 17275856 |
| Metalloproteases (Crovidisin, Jararhagin, LeucurolysinB, TSVDM) | Pro-Apoptotic | Antitumor | Shows inhibition of melanoma cells and proapoptotic effect, interfering with the adhesion mechanisms. Apoptosis, inhibitor of cell proliferation and inducer of cell's morphologic changes | Crotalus viridis, Bothrops jararaca, Bothrops leucurus, Trimeresurus stejnegeri | 24683541, 9016825, 12175610, 21539897 |
| Disintigrins (Contortrostatin, Leucurogin, Saxatilin, Obtustatin, Adinbitor, Rhodocetin, Salmosin, Trigramin, Triflavin, Rhodostomin, Echistatin) | Peptide toxin | Antitumor, Anti-angiogenic, Anti-invasive, Anti-adhesive | Anti-invasive and anti-adhesive activities on tumor cells and endothelial cells. Inhibits the cell adhesion, migration, and collagen contraction. Inhibits the adhesion of melanoma cells to extracellular matrix components | Agkistrodon contortrix contortrix, Bothrops leucurus, Gloydius saxatilis, Vipera lebetina, Agkistrodon halys stejneger, Calloselasma rhodostoma, Agkistrodon halys brevicaudus, Trimeresurus gramineus, Trimeresurus flavoviridis, Agkistrodon rhodostoma | 24683541, 7735124, 11025252, 15987550, 15041797, 14517425, 16487560, 14713370, 8695278, 21641921, 15188058, 10446992, 11910185, 10944460, 15644794, 7841039, 9457071, 14977354, 16286995, 1879472 |
| Serine proteases (Crotalase, Batroxobin) | Cytotoxic | Antitumor | Inhibits tumor growth | Crotalus adamanteus, Bothrops moojeni | 24683541, 3538422, 18830584 |
| Peptides (Cardiotoxin III, Cytotoxin P4, Cathelicidin-BF, Lectins) | Cytotoxic | Antitumor, Anti-invasive | Blocks migration and invasion of breast cancer cells. Cytotoxic effects and inhibits cell adhesion, Inhibits angiogenesis | Naja naja atra, Naja naja nigricollis, Bungarus fasciatus, Bothrophs jararacusus, Macrovipera labetina, Echis multisquamatus | 24683541, 11137138, 15763081, 1419110, 1772420, 1440650, 10933804, 24683541, 11478954, 17300927, 12475639 |
| Alpha-fibrinogenase (Chymotrypsin-like protease VLCTLP, Zinc metalloproteinase-disintegrin-like, Bradykinin-releasing enzyme KR-E-1, metalloproteinase, Thrombin-like enzyme ancrod, Snaclec anticoagulant protein A/B, Snaclec coagulation factor IX/factor X-binding protein subu | Proteolytic activity | Anti-coagulant | Degrades alpha and beta chains of fibrinogen (FGA), and has strong caseinolytic activity, inhibit platelet aggregation. Releases bradykinin from bovine HMW kininogen. This metalloproteinase displays proteolytic activity on fibrin, fibrinogen, collagen, ca | Macrovipera lebetina, Crotalus adamanteus, Protobothrops jerdonii, Bothrops moojeni, Gloydius ussuriensis, Bothrops jararacussu, Calloselasma rhodostoma, Deinagkistrodon acutus, Protobothrops flavoviridis, Bothrops jararaca, Hydrophis schistosus, Notechis | 20186872, 14511668, 19732785, 22975266, 20950666, 3201479, 18006118, 1544412, 12175618, 11404471, 1831197, 2613688, 10558903, 15925567, 9346315, 8399228, 8703912, 9657441, 11051105, 11910195, 11858489, 16707920, 3117784, 1002692, 9604284, 1899180, 2781572 |
| Phospholipase A2 (crotoxin basic subunit CBc, acidic phospholipaseA2) | Pro- and anti-inflammatory | Anti-inflammatory | This enzyme has been shown to induce the release of some pro- and anti-inflammatory cytokines | Crotalus durissu scollilineatus, Bothrops leucurus | 16003952, 17915277, 21699995 |
| Cathelicidin-related antimicrobial peptide | Bactericidal activity | Anti-micorbial | Potent antimicrobial peptide against most of Gram-negative and some Gram-positive bacteria and some fungi. Adopts an amphipathic alpha helical conformation that allows to partition into the target membrane. No hemolytic and cytotoxic activities have been | Bungarus fasciatus, Pseudonaja textilis | 18795096, 25100358 |
| Zinc metalloproteinase-disintegrin-like | Bactericidal activity | Anti-micorbial | It shows bactericidal activity against E. coli and S. aureus | Bothrops jararacussu | 17081786, 15246772 |
| Basic phospholipase A2 | Bactericidal activity | Anti-micorbial | It shows bactericidal activities against both Gram-negative and -positive bacteria | Bungarus fasciatus, Crotalus durissus ruruima, Bothrops pauloensis, Bothrops jararacussu, Bothrops moojeni, Crotalus durissus collilineatus | 17383773, 19013478, 10860537, 9972319, 3176051, 11018293, 11829743 |
| Acidic phospholipase A2 | Bactericidal activity | Anti-micorbial | It shows a strong antimicrobial activity against Gram-negative bacteria | Bothrops jararacussu, Bothrops moojeni, Crotalus durissus collilineatus, Bothrops atrox | 15214498, 12167491, 22571953, 16003952, 15225567 |
| C-type lectinBpLec | Bactericidal activity | Anti-micorbial | It inhibits gram positive (S. aureus) | Bothrops pauloensis | 23178369 |
| L-amino-acid oxidase (ACTX-8, Cdc18) | Bactericidal activity | Anti-micorbial | It shows activities against both Gram-positive and Gram-negative bacteria. It binds to bacteria and shows antibacterial activities by generating hydrogen peroxide. In general, binding and antibacterial activities are higher against Gram-positive than agai | Pseudechis australis, Notechis scutatus scutatus, Demansia vestigiata, Crotalus atrox, Bungarus fasciatus, Gloydius blomhoffii, Bothrops atrox, Ophiophagus hannah, Bothrops jararaca, Deinagkistrodon acutus, Crotalus durissus cumanensis | 1796476, 16261251, 17275856, 9083096, 11341935, 8694800, 19393676, 18804547, 21300133, 17543361, 9304806, 18346051, 19101583, 20615423, 18346051, 23287728 |
| Serine proteases (Metalloprotease inhibitor, Thrombin-like enzyme crotalase, Fibrinogen-clotting enzyme) | Plasminogen activator | Anti- hypertensive | Serine protease activates plasminogen. Weakly hydrolyzes the alpha chain of human fibrinogen without releasing fibrinopeptide A. Does not hydrolyze plasma kallikrein or factor Xa. Does not clot fibrinogen. Does not affect platelet function. Thrombin-like | Lachesi smutamuta, Echis ocellatus, Crotalus adamanteus | 17034951, 18029259, 1014024, 5132665 |
| Cytotoxin 1 | Bactericidal activity | Anti-micorbial | Cytotoxicity | Anti-arthritic, Anti-inflammatory | 20595038 |
| Cytotoxin 1 | Cytotoxicity | Anti-arthritic, Anti-inflammatory | Produces irreversible complete blockade of auricular contractionmat high concentrations. Possess anti-arthritic and anti-inflammatory potential. Shows no cytolytic activity | Naja kaouthia | 20595038 |
| Alpha-elapitoxin-(Nk2a, Nno2a.Ls2a) | Neurotoxicity | Neurotoxin | The monomeric form binds with high affinity to muscular and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (nAChR). Causes paralysis by preventing acetylcholine binding to the nAChR. The homodimeric form binds with low affinity to muscular and | Naja kaouthia, Naja oxiana, Laticauda semifasciata | 18381281, 6771288, 6553056, 2086254, 9053737, 9305882, 9840221, 10574958, 10852927, 18067132, 11867717, 6930640, 2279844, 1317211, 12133834, 15791209, 9920490, 12957382, 4616684, 8555211 |
| Short neurotoxin (A,B, C, D) | Neurotoxicity | Neurotoxin | Binds to muscle nicotinic acetylcholine receptor (nAChR) and inhibit acetylcholine from binding to the receptor, thereby impairing neuromuscular transmission | Hydrophis schistosus, Naja oxiana, Naja annulifera, Naja pallid, Naja mossambica, Naja nivea, Hydrophis lapemoides, Aipysurus laevis, Dendroaspis polylepis polylepis, Dendroaspis viridis | 4850498, 4747603, 8504813, 923577, 9305882, 1332755, 12538890, 6615431, 4995745, 5033401, 2847926, 1433289, 4091794, 4112538 |
| Short neurotoxin (1,2, 3,4,5,6, 7) (OH-35, OKI-Ed) | Neurotoxicity | Neurotoxin | Binds with high affinity to muscle nicotinic acetylcholine receptor (nAChR) and hinders acetylcholine binding to the receptor, thereby impairing neuromuscular transmission. Competes with the binding of alpha-bungarotoxin on muscle AChR (from Torpedo) with | Pseudonaja textilis, Hydrophis cyanocinctus | 10518793, 10818230, 16284125, 4830190, 8447823, 4855008, 21133350, 10497260 |
| Long neurotoxin (1, 2, 3,4, 20) Long neurotoxin homolog (Pa ID, OH-5, OH-56, OH-37, OH-34) | Neurotoxicity | Neurotoxin | Binds with high affinity to muscular nicotinic acetylcholine receptors (nAChRs), whereas it binds with a low affinity. Inhibits carbachol-induced muscle contraction in a reversible manner | Ophiophagus Hannah, Demansia vestigiata, Drysdalia coronoides, Pseudechis australis, Naja anchietae | 14559085, 16284125, 16261251, 5033401 |
| Weak neurotoxin (5,6,8,10, WNTX34, NNAM2) | Neurotoxicity | Neurotoxin | Binds with low affinity to muscular (alpha-1-beta-1-epsilon-delta/CHRNA1-CHRNB1-CHRNE-CHRND) and very low affinity to neuronal (alpha7) nicotinic acetylcholine receptor | Naja sputatrix, Ophiophagus hannah, Naja atra, Laticauda semifasciata | 9838137, 12199703, 14572646, 16689684, 24297900, 2060629 |
| Kappa-2/3-bungarotoxin | Neurotoxicity | Neurotoxin | Postsynaptic neurotoxin that binds and inhibits neuronal nicotinic acetylcholine receptors (nAChR) with high affinity (IC50<100 nM). Is a selective, and slowly reversible antagonist of alpha-3/CHRNA3-containing and some alpha-4/CHRNA4-containing AChRs | Bungarus multicinctus | 2315018, 12403176, 2322821 |
| Erabutoxin (a, b,c) | Neurotoxicity | Neurotoxin | Binds with high affinity to muscular nicotinic acetylcholine receptors (nAChRs) and with low affinity to neuronal alpha-7 nAChRs and inhibit acetylcholine from binding to the receptor, thereby impairing neuromuscular transmission. Produces peripheral para | Laticauda semifasciata | 9305882, 9840221, 2249684, 12957382, 4664580, 5166329, 588261 |
| Cobrotoxin (II, b, c) | Neurotoxicity | Neurotoxin | Binds to muscle nicotinic acetylcholine receptor (nAChR) and inhibit acetylcholine from binding to the receptor, thereby impairing neuromuscular transmission. Has a higher toxicity than cobrotoxin-b. Produces peripheral paralysis by blocking neuromuscular | Naja atra, Naja kaouthia | 9367842, 5820687, 8448165, 5533659, 12039691, 11904231 |
| Cysteine-rich protein (pseudecin, LEI1, pseudechetoxin-like, ablomin, trifling, ophanin, catrin) | Neurotoxicity | Neurotoxin | Blocks olfactory (CNGA2) and retinal (CNGA1) CNG channel currents. Blocks contraction of smooth muscle elicited by high potassium-induced depolarization, but does not block caffein-stimulated contraction. May target voltage-gated calcium channels on smoot | Pseudechis porphyriacus, Philodryas olfersii, Trimeresurus stejnegeri, Leioheterodon madagascariensis, Pseudonaja textilis, Gloydius blomhoffii, Protobothrops flavoviridis, Ophiophagus Hannah, Crotalus atrox | 12234174, 16857193, 16292255, 24297900, 16261251, 16284125 |
| Taicatoxin, alpha-neurotoxin-like component | Neurotoxicity | Neurotoxin | The heterotrimer blocks the voltage-dependent L-type calcium channels (Cav1/CACNA1) from the heart, and the small conductance calcium-activated potassium channels (KCa2/KCNN) in the chromaffin cells and in the brain | Oxyuranus scutellatus | 8901456, 9242659, 15855042 |
| Dendrotoxin (A/B) | Neurotoxicity | Dendrotoxin | Inhibits acetylcholinesterase. Has been described to inhibit both the slowly and the rapidly inactivating phases of potassium efflux. | Dendroaspis angusticeps | 1304870 |
| Kunitz-type serine protease inhibitor homolog dendrotoxin (I/K/E/A) | Neurotoxicity | Dendrotoxin | Serine protease inhibitor homolog that blocks voltage-gated potassium channels and facilitates neurotransmitter release. Binds transition metal ions such as copper and cobalt. | Dendroaspis polylepis polylepis, Dendroaspis angusticeps | 8612784, 10698633 10429207, 913421, 10936620, 23771044, 668688 |
| Cytotoxin (1-7) | Cytotoxicity | Cytotoxin | Basic protein that binds to cell membrane and depolarizes cardiomyocytes. It also possesses lytic activity on many other cells, including red blood cells. | Naja mossambica, Naja atra, Naja pallid, Naja kaouthia | 8619792, 10708798, 5518165, 955081, 8448165, 8182052, 9245415, 15184042, 15922335, 16263708, 16407244, 17685633, 17714752, 8308891, 11669614, 12660250, 15590643 |
| Beta-cardiotoxin CTX | Cytotoxin | Cytotoxicity | Acts as a beta-blocker by binding to beta-1 and beta-2 adrenergic receptors and can dose dependently decrease the heart rate | Ophiophagus hannah | 15302536, 16689684, 24297900 |
| Cytotoxin 1a/1b (Cardiotoxin-1a/1b) | Cytotoxin | Cytotoxicity | Shows cytolytic activity on many different cells by forming pore in lipid membranes. | Naja atra | |
| Cardiotoxin-like basic polypeptide (Bibrotoxin, Haditoxin, Cytotoxin KJC3, Toxin FS-2, Sarafotoxin) | Cytolytic, Vasoconstriction | Cytotoxicity | These toxins cause cardiac arrest as a result of coronary vasospasm. Antagonist of muscle (alpha/ beta/ gamma/ delta) and neuronal. Shows cytolytic activity on many different cells by forming pore in lipid membranes. Specific blocker of the voltage-depend | Naja atra, Atractaspis bibronii, Ophiophagus hannah, Naja sputatrix, Atractaspis engaddensis | 17277458, 8416802, 17616557, 880951, 8826098, 9636051, 7727450, 8428983, 3176048, 2845579, 1339278, 21889567, 2037041, 20504727, 7849060 |