Skip to main content

Snake venom toxins: toxicity and medicinal applications

Applied Microbiology and Biotechnology volume 100, pages 6165–6181 (2016)Cite this article

Abstract

Snake venoms are complex mixtures of small molecules and peptides/proteins, and most of them display certain kinds of bioactivities. They include neurotoxic, cytotoxic, cardiotoxic, myotoxic, and many different enzymatic activities. Snake envenomation is a significant health issue as millions of snakebites are reported annually. A large number of people are injured and die due to snake venom poisoning. However, several fatal snake venom toxins have found potential uses as diagnostic tools, therapeutic agent, or drug leads. In this review, different non-enzymatically active snake venom toxins which have potential therapeutic properties such as antitumor, antimicrobial, anticoagulating, and analgesic activities will be discussed.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  • Adade CM, Carvalho AL, Tomaz MA, Costa TF, Godinho JL, Melo PA, Lima AP, Rodrigues JC, Zingali RB, Souto-Padron T (2014) Crovirin, a snake venom cysteine-rich secretory protein (CRISP) with promising activity against Trypanosomes and Leishmania. PLoS Negl Trop Dis 8(10):e3252. doi:10.1371/journal.pntd.0003252

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Adler M, Lazarus RA, Dennis MS, Wagner G (1991) Solution structure of kistrin, a potent platelet aggregation inhibitor and GP IIb-IIIa antagonist. Science 253(5018):445–448

    CAS  PubMed  Article  Google Scholar 

  • Andersen JC (2004) Advances in anticoagulation therapy: the role of selective inhibitors of factor Xa and thrombin in thromboprophylaxis after major orthopedic surgery. Semin Thromb Hemost 30(6):609–618. doi:10.1055/s-2004-861502

    CAS  PubMed  Article  Google Scholar 

  • Bell WR Jr (1997) Defibrinogenating enzymes. Drugs 54(Suppl 3):18–30, discussion 30–1

    CAS  PubMed  Article  Google Scholar 

  • Bilgrami S, Tomar S, Yadav S, Kaur P, Kumar J, Jabeen T, Sharma S, Singh TP (2004) Crystal structure of schistatin, a disintegrin homodimer from saw-scaled viper (Echis carinatus) at 2.5 Å resolution. J Mol Biol 341(3):829–837. doi:10.1016/j.jmb.2004.06.048

    CAS  PubMed  Article  Google Scholar 

  • Blacklow B, Kornhauser R, Hains PG, Loiacono R, Escoubas P, Graudins A, Nicholson GM (2011) α-Elapitoxin-Aa2a, a long-chain snake α-neurotoxin with potent actions on muscle (α1)(2)βγδ nicotinic receptors, lacks the classical high affinity for neuronal α7 nicotinic receptors. Biochem Pharmacol 81(2):314–325. doi:10.1016/j.bcp.2010.10.004

    CAS  PubMed  Article  Google Scholar 

  • Brahma RK, McCleary RJ, Kini RM, Doley R (2015) Venom gland transcriptomics for identifying, cataloging, and characterizing venom proteins in snakes. Toxicon 93:1–10. doi:10.1016/j.toxicon.2014.10.022

    CAS  PubMed  Article  Google Scholar 

  • Calvete JJ (2014) Next-generation snake venomics: protein-locus resolution through venom proteome decomplexation. Expert Rev Proteomics 11(3):315–329. doi:10.1586/14789450.2014.900447

    CAS  PubMed  Article  Google Scholar 

  • Casewell NR, Wuster W, Vonk FJ, Harrison RA, Fry BG (2013) Complex cocktails: the evolutionary novelty of venoms. Trends Ecol Evol 28(4):219–229. doi:10.1016/j.tree.2012.10.020

    PubMed  Article  Google Scholar 

  • Chaisakul J, Parkington HC, Isbister GK, Konstantakopoulos N, Hodgson WC (2013) Differential myotoxic and cytotoxic activities of pre-synaptic neurotoxins from Papuan taipan (Oxyuranus scutellatus) and Irian Jayan death adder (Acanthophis rugosus) venoms. Basic Clin Pharmacol Toxicol 112(5):325–334. doi:10.1111/bcpt.12048

    CAS  PubMed  Article  Google Scholar 

  • Chang LS, Chung C, Wu BN, Yang CC (2002) Characterization and gene organization of Taiwan banded krait (Bungarus multicinctus) gamma-bungarotoxin. J Protein Chem 21(4):223–229

    CAS  PubMed  Article  Google Scholar 

  • Chang LS, Wang JJ, Cheng YC, Chou WM (2008) Genetic organization of Bungarus multicinctus protease inhibitor-like proteins. Toxicon 51(8):1490–1495. doi:10.1016/j.toxicon.2008.03.025

    CAS  PubMed  Article  Google Scholar 

  • Chen R, Robinson SE (1990) The effect of cholinergic manipulations on the analgesic response to cobrotoxin in mice. Life Sci 47(21):1949–1954

    CAS  PubMed  Article  Google Scholar 

  • Chen LW, Kao PH, Fu YS, Lin SR, Chang LS (2011) Membrane-damaging activity of Taiwan cobra cardiotoxin 3 is responsible for its bactericidal activity. Toxicon 58(1):46–53. doi:10.1016/j.toxicon.2011.04.021

    CAS  PubMed  Article  Google Scholar 

  • Chen PC, Hayashi MA, Oliveira EB, Karpel RL (2012) DNA-interactive properties of crotamine, a cell-penetrating polypeptide and a potential drug carrier. PLoS One 7(11):e48913. doi:10.1371/journal.pone.0048913

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Cheng C-H, Chen Y-C, Shiu J-H, Chang Y-T, Chang Y-S, Huang C-H, Chen C-Y, Chuang W-J (2012) Dynamics and functional differences between dendroaspin and rhodostomin: insights into protein scaffolds in integrin recognition. Protein Sci 21(12):1872–1884. doi:10.1002/pro.2169

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Chippaux JP, Williams V, White J (1991) Snake venom variability: methods of study, results and interpretation. Toxicon 29(11):1279–1303

    CAS  PubMed  Article  Google Scholar 

  • Chou KC (2004) Structural bioinformatics and its impact to biomedical science. Curr Med Chem 11(16):2105–2134

    CAS  PubMed  Article  Google Scholar 

  • Cousin X, Creminon C, Grassi J, Meflah K, Cornu G, Saliou B, Bon S, Massoulie J, Bon C (1996) Acetylcholinesterase from Bungarus venom: a monomeric species. FEBS Lett 387(2–3):196–200

    CAS  PubMed  Article  Google Scholar 

  • Das B, Sarkar C, Shankar PR (2007) Pretreatment with sarafotoxin 6c prior to coronary occlusion protects against infarction and arrhythmias via cardiomyocyte mitochondrial K(ATP) channel activation in the intact rabbit heart during ischemia/reperfusion. Cardiovasc Drugs Ther 21(4):243–251. doi:10.1007/s10557-007-6031-5

    CAS  PubMed  Article  Google Scholar 

  • Das T, Bhattacharya S, Biswas A, Gupta SD, Gomes A (2013) Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP-2 and MMP-9 activities by cytotoxin protein NN-32 purified from Indian spectacled cobra (Naja naja) venom. Toxicon 65:1–4. doi:10.1016/j.toxicon.2013.01.004

    CAS  PubMed  Article  Google Scholar 

  • de Oliveira Junior NG, e Silva Cardoso MH, Franco OL (2013) Snake venoms: attractive antimicrobial proteinaceous compounds for therapeutic purposes. Cell Mol Life Sci 70(24):4645–4658. doi:10.1007/s00018-013-1345-x

    PubMed  Article  CAS  Google Scholar 

  • Debnath A, Saha A, Gomes A, Biswas S, Chakrabarti P, Giri B, Biswas AK, Gupta SD (2010) A lethal cardiotoxic-cytotoxic protein from the Indian monocellate cobra (Naja kaouthia) venom. Toxicon 56(4):569–579. doi:10.1016/j.toxicon.2010.05.016

    CAS  PubMed  Article  Google Scholar 

  • Del Brutto OH, Del Brutto VJ (2012) Neurological complications of venomous snake bites: a review. Acta Neurol Scand 125(6):363–372. doi:10.1111/j.1600-0404.2011.01593.x

    PubMed  Article  CAS  Google Scholar 

  • Deval E, Lingueglia E (2015) Acid-sensing ion channels and nociception in the peripheral and central nervous systems. Neuropharmacology 94:49–57. doi:10.1016/j.neuropharm.2015.02.009

    CAS  PubMed  Article  Google Scholar 

  • Diochot S, Baron A, Salinas M, Douguet D, Scarzello S, Dabert-Gay AS, Debayle D, Friend V, Alloui A, Lazdunski M, Lingueglia E (2012) Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature 490(7421):552–555. doi:10.1038/nature11494

    CAS  PubMed  Article  Google Scholar 

  • Diochot S, Alloui A, Rodrigues P, Dauvois M, Friend V, Aissouni Y, Eschalier A, Lingueglia E, Baron A (2016) Analgesic effects of mambalgin peptide inhibitors of acid-sensing ion channels in inflammatory and neuropathic pain. Pain 157(3):552–559. doi:10.1097/j.pain.0000000000000397

    CAS  PubMed  Article  Google Scholar 

  • Dubovskii PV, Utkin YN (2015) Antiproliferative activity of cobra venom cytotoxins. Curr Top Med Chem 15(7):638–648

    CAS  PubMed  Article  Google Scholar 

  • Ducancel F (2005) Endothelin-like peptides. Cell Mol Life Sci 62(23):2828–2839. doi:10.1007/s00018-005-5286-x

    CAS  PubMed  Article  Google Scholar 

  • Dufton MJ (1992) Venomous mammals. Pharmacol Ther 53(2):199–215

    CAS  PubMed  Article  Google Scholar 

  • Duggan PJ, Tuck KL (2015) Bioactive mimetics of conotoxins and other venom peptides. Toxins (Basel) 7(10):4175–4198. doi:10.3390/toxins7104175

    CAS  Article  Google Scholar 

  • Dutertre S (2014) Venomics in medicinal chemistry. Future Med Chem 6(15):1609–1610. doi:10.4155/fmc.14.117

    CAS  PubMed  Article  Google Scholar 

  • Earl ST, Birrell GW, Wallis TP, St Pierre LD, Masci PP, de Jersey J, Gorman JJ, Lavin MF (2006) Post-translational modification accounts for the presence of varied forms of nerve growth factor in Australian elapid snake venoms. Proteomics 6(24):6554–6565. doi:10.1002/pmic.200600263

    CAS  PubMed  Article  Google Scholar 

  • Feofanov AV, Sharonov GV, Astapova MV, Rodionov DI, Utkin YN, Arseniev AS (2005) Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage. Biochem J 390(Pt 1):11–18. doi:10.1042/BJ20041892

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Fox JW, Serrano SM (2005) Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases. Toxicon 45(8):969–985. doi:10.1016/j.toxicon.2005.02.012

    CAS  PubMed  Article  Google Scholar 

  • Fox JW, Elzinga M, Tu AT (1979) Amino acid sequence and disulfide bond assignment of myotoxin a isolated from the venom of Prairie rattlesnake (Crotalus viridis viridis). Biochemistry 18(4):678–684

    CAS  PubMed  Article  Google Scholar 

  • French R, Brooks D, Ruha AM, Shirazi F, Chase P, Boesen K, Walter F (2015) Gila monster (Heloderma suspectum) envenomation: descriptive analysis of calls to United States Poison Centers with focus on Arizona cases. Clin Toxicol (Phila) 53(1):60–70. doi:10.3109/15563650.2014.988791

    Article  Google Scholar 

  • Gasanov SE, Alsarraj MA, Gasanov NE, Rael ED (1997) Cobra venom cytotoxin free of phospholipase A2 and its effect on model membranes and T leukemia cells. J Membr Biol 155(2):133–142

    CAS  PubMed  Article  Google Scholar 

  • Gasanov SE, Dagda RK, Rael ED (2014) Snake venom cytotoxins, phospholipase As, and Zn-dependent metalloproteinases: mechanisms of action and pharmacological relevance. J Clin Toxicol 4(1):1000181

    PubMed  PubMed Central  Google Scholar 

  • Georgieva D, Arni RK, Betzel C (2008) Proteome analysis of snake venom toxins: pharmacological insights. Expert Rev Proteomics 5(6):787–797. doi:10.1586/14789450.5.6.787

    CAS  PubMed  Article  Google Scholar 

  • Gomes MS, de Queiroz MR, Mamede CC, Mendes MM, Hamaguchi A, Homsi-Brandeburgo MI, Sousa MV, Aquino EN, Castro MS, de Oliveira F, Rodrigues VM (2011) Purification and functional characterization of a new metalloproteinase (BleucMP) from Bothrops leucurus snake venom. Comp Biochem Physiol C Toxicol Pharmacol 153(3):290–300. doi:10.1016/j.cbpc.2010.11.008

    PubMed  Article  CAS  Google Scholar 

  • Gould RJ, Polokoff MA, Friedman PA, Huang TF, Holt JC, Cook JJ, Niewiarowski S (1990) Disintegrins: a family of integrin inhibitory proteins from viper venoms. Proc Soc Exp Biol Med 195(2):168–171

    CAS  PubMed  Article  Google Scholar 

  • Gutierrez JM, Cerdas L (1984) Mechanism of action of myotoxins isolated from snake venoms. Rev Biol Trop 32(2):213–222

    CAS  PubMed  Google Scholar 

  • Halford ZA, Yu PY, Likeman RK, Hawley-Molloy JS, Thomas C, Bingham JP (2015) Cone shell envenomation: epidemiology, pharmacology and medical care. Diving Hyperb Med 45(3):200–207

    PubMed  Google Scholar 

  • Harvey AL (2013) Chapter 62: snake peptides. In: Kastin AJ (ed) Handbook of biologically active peptides, 2nd edn. Academic, Boston, pp 451–460

    Chapter  Google Scholar 

  • Harvey AL (2014) Toxins and drug discovery. Toxicon 92:193–200. doi:10.1016/j.toxicon.2014.10.020

    CAS  PubMed  Article  Google Scholar 

  • Harvey AL, Robertson B (2004) Dendrotoxins: structure-activity relationships and effects on potassium ion channels. Curr Med Chem 11(23):3065–3072

    CAS  PubMed  Article  Google Scholar 

  • Hashemzadeh M, Furukawa M, Goldsberry S, Movahed MR (2008) Chemical structures and mode of action of intravenous glycoprotein IIb/IIIa receptor blockers: a review. Exp Clin Cardiol 13(4):192–197

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hennerici MG, Kay R, Bogousslavsky J, Lenzi GL, Verstraete M, Orgogozo JM (2006) Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial. Lancet 368(9550):1871–1878. doi:10.1016/S0140-6736(06)69776-6

    CAS  PubMed  Article  Google Scholar 

  • Hodgson WC, Isbister GK (2009) The application of toxins and venoms to cardiovascular drug discovery. Curr Opin Pharmacol 9(2):173–176. doi:10.1016/j.coph.2008.11.007

    CAS  PubMed  Article  Google Scholar 

  • Huang P, Mackessy SP (2004) Biochemical characterization of phospholipase A2 (trimorphin) from the venom of the Sonoran Lyre Snake Trimorphodon biscutatus lambda (family Colubridae). Toxicon 44(1):27–36. doi:10.1016/j.toxicon.2004.03.027

    CAS  PubMed  Article  Google Scholar 

  • Jain D, Kumar S (2012) Snake venom: a potent anticancer agent. Asian Pac J Cancer Prev 13(10):4855–4860

    PubMed  Article  Google Scholar 

  • Jang SH, Ryu PD, Lee SY (2011) Dendrotoxin-k suppresses tumor growth induced by human lung adenocarcinoma A549 cells in nude mice. J Vet Sci 12(1):35–40

    PubMed  PubMed Central  Article  Google Scholar 

  • Jared C, Mailho-Fontana PL, Antoniazzi MM, Mendes VA, Barbaro KC, Rodrigues MT, Brodie ED Jr (2015) Venomous frogs use heads as weapons. Curr Biol 25(16):2166–2170. doi:10.1016/j.cub.2015.06.061

    CAS  PubMed  Article  Google Scholar 

  • Jouiaei M, Yanagihara AA, Madio B, Nevalainen TJ, Alewood PF, Fry BG (2015) Ancient venom systems: a review on cnidaria toxins. Toxins (Basel) 7(6):2251–2271. doi:10.3390/toxins7062251

    CAS  Article  Google Scholar 

  • Junqueira-de-Azevedo IL, Ching AT, Carvalho E, Faria F, Nishiyama MY Jr, Ho PL, Diniz MR (2006) Lachesis muta (Viperidae) cDNAs reveal diverging pit viper molecules and scaffolds typical of cobra (Elapidae) venoms: implications for snake toxin repertoire evolution. Genetics 173(2):877–889. doi:10.1534/genetics.106.056515

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Kaas Q, Craik DJ (2015) Bioinformatics-aided venomics. Toxins (Basel) 7(6):2159–2187. doi:10.3390/toxins7062159

    CAS  Article  Google Scholar 

  • Kao PH, Lin SR, Hu WP, Chang LS (2012) Naja naja atra and Naja nigricollis cardiotoxins induce fusion of Escherichia coli and Staphylococcus aureus membrane-mimicking liposomes. Toxicon 60(3):367–377. doi:10.1016/j.toxicon.2012.04.345

    CAS  PubMed  Article  Google Scholar 

  • Kenneth VK, Scott AW, Tamara LS (2009) Reptile venom glands. In: Mackessy SP (ed) Handbook of venoms and toxins of reptiles. CRC, Boca Raton, pp 65–66

    Google Scholar 

  • Kerkis I, Silva Fde S, Pereira A, Kerkis A, Radis-Baptista G (2010) Biological versatility of crotamine—a cationic peptide from the venom of a South American rattlesnake. Expert Opin Investig Drugs 19(12):1515–1525. doi:10.1517/13543784.2010.534457

    CAS  PubMed  Article  Google Scholar 

  • Kini RM (2002) Molecular moulds with multiple missions: functional sites in three-finger toxins. Clin Exp Pharmacol Physiol 29(9):815–822

    CAS  PubMed  Article  Google Scholar 

  • Kini RM (2003) Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes. Toxicon 42(8):827–840. doi:10.1016/j.toxicon.2003.11.002

    CAS  PubMed  Article  Google Scholar 

  • Kini RM, Doley R (2010) Structure, function and evolution of three-finger toxins: mini proteins with multiple targets. Toxicon 56(6):855–867. doi:10.1016/j.toxicon.2010.07.010

    CAS  PubMed  Article  Google Scholar 

  • Koh CY, Kini RM (2012) From snake venom toxins to therapeutics—cardiovascular examples. Toxicon 59(4):497–506. doi:10.1016/j.toxicon.2011.03.017

    CAS  PubMed  Article  Google Scholar 

  • Koh DCI, Armugam A, Jeyaseelan K (2006) Snake venom components and their applications in biomedicine. Cell Mol Life Sci 63(24):3030–3041. doi:10.1007/s00018-006-6315-0

    CAS  PubMed  Article  Google Scholar 

  • Komori K, Konishi M, Maruta Y, Toriba M, Sakai A, Matsuda A, Hori T, Nakatani M, Minamino N, Akizawa T (2006) Characterization of a novel metalloproteinase in Duvernoy’s gland of Rhabdophis tigrinus tigrinus. J Toxicol Sci 31(2):157–168

    CAS  PubMed  Article  Google Scholar 

  • Konshina AG, Boldyrev IA, Utkin YN, Omel’kov AV, Efremov RG (2011) Snake cytotoxins bind to membranes via interactions with phosphatidylserine head groups of lipids. PLoS One 6(4):e19064. doi:10.1371/journal.pone.0019064

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Kularatne SA, Senanayake N (2014) Venomous snake bites, scorpions, and spiders. Handb Clin Neurol 120:987–1001. doi:10.1016/B978-0-7020-4087-0.00066-8

    CAS  PubMed  Article  Google Scholar 

  • Lecht S, Chiaverelli RA, Gerstenhaber J, Calvete JJ, Lazarovici P, Casewell NR, Harrison R, Lelkes PI, Marcinkiewicz C (2015) Anti-angiogenic activities of snake venom CRISP isolated from Echis carinatus sochureki. Biochim Biophys Acta 1850(6):1169–1179. doi:10.1016/j.bbagen.2015.02.002

    CAS  PubMed  Article  Google Scholar 

  • Levy DE, Trammel J, Wasiewski WW (2009) Ancrod for acute ischemic stroke: a new dosing regimen derived from analysis of prior ancrod stroke studies. J Stroke Cerebrovasc Dis 18(1):23–27. doi:10.1016/j.jstrokecerebrovasdis.2008.07.009

    PubMed  Article  Google Scholar 

  • Li S, Ji H, Cheng X, Li BX, Ng TB (2000) Antithrombotic and thrombolytic activities of agkisacutacin, a snake venom proteinase, in experimental models. Gen Pharmacol 35(4):179–187

    CAS  PubMed  Article  Google Scholar 

  • Liberio MS, Joanitti GA, Fontes W, Castro MS (2013) Anticancer peptides and proteins: a panoramic view. Protein Pept Lett 20(4):380–391

    CAS  PubMed  Google Scholar 

  • Liu S, Marder VJ, Levy DE, Wang SJ, Yang F, Paganini-Hill A, Fisher MJ (2011) Ancrod and fibrin formation: perspectives on mechanisms of action. Stroke 42(11):3277–3280. doi:10.1161/STROKEAHA.111.622753

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Liu CC, Yang H, Zhang LL, Zhang Q, Chen B, Wang Y (2014) Biotoxins for cancer therapy. Asian Pac J Cancer Prev 15(12):4753–4758

    PubMed  Article  Google Scholar 

  • Lodha A, Kamaluddeen M, Akierman A, Amin H (2011) Role of hemocoagulase in pulmonary hemorrhage in preterm infants: a systematic review. Indian J Pediatr 78(7):838–844. doi:10.1007/s12098-010-0326-4

    PubMed  Article  Google Scholar 

  • Macedo SR, de Barros NB, Ferreira AS, Moreira-Dill LS, Calderon LA, Soares AM, Nicolete R (2015) Biodegradable microparticles containing crotamine isolated from Crotalus durissus terrificus display antileishmanial activity in vitro. Pharmacology 95(1–2):78–86. doi:10.1159/000371391

    CAS  PubMed  Article  Google Scholar 

  • Mancin AC, Soares AM, Andriao-Escarso SH, Faca VM, Greene LJ, Zuccolotto S, Pela IR, Giglio JR (1998) The analgesic activity of crotamine, a neurotoxin from Crotalus durissus terrificus (South American rattlesnake) venom: a biochemical and pharmacological study. Toxicon 36(12):1927–1937

    CAS  PubMed  Article  Google Scholar 

  • Marchot P, Prowse CN, Kanter J, Camp S, Ackermann EJ, Radic Z, Bougis PE, Taylor P (1997) Expression and activity of mutants of fasciculin, a peptidic acetylcholinesterase inhibitor from mamba venom. J Biol Chem 272(6):3502–3510

    CAS  PubMed  Article  Google Scholar 

  • McCleary RJ, Kini RM (2013) Non-enzymatic proteins from snake venoms: a gold mine of pharmacological tools and drug leads. Toxicon 62:56–74. doi:10.1016/j.toxicon.2012.09.008

    CAS  PubMed  Article  Google Scholar 

  • McDowell RS, Dennis MS, Louie A, Shuster M, Mulkerrin MG, Lazarus RA (1992) Mambin, a potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor structurally related to the short neurotoxins. Biochemistry 31(20):4766–4772

    CAS  PubMed  Article  Google Scholar 

  • McKie PM, Sangaralingham SJ, Burnett JC Jr (2010) CD-NP: an innovative designer natriuretic peptide activator of particulate guanylyl cyclase receptors for cardiorenal disease. Curr Heart Fail Rep 7(3):93–99. doi:10.1007/s11897-010-0016-6

    CAS  PubMed  Article  Google Scholar 

  • Mundy HR, Jones SJ, Hobart JC, Hanna MG, Lee PJ (2003) A randomized controlled study of modified cobratoxin in adrenomyeloneuropathy. Neurology 61(4):528–530

    CAS  PubMed  Article  Google Scholar 

  • Nascimento FD, Sancey L, Pereira A, Rome C, Oliveira V, Oliveira EB, Nader HB, Yamane T, Kerkis I, Tersariol IL, Coll JL, Hayashi MA (2012) The natural cell-penetrating peptide crotamine targets tumor tissue in vivo and triggers a lethal calcium-dependent pathway in cultured cells. Mol Pharm 9(2):211–221. doi:10.1021/mp2000605

    CAS  PubMed  Article  Google Scholar 

  • Nguyen TT, Folch B, Letourneau M, Vaudry D, Truong NH, Doucet N, Chatenet D, Fournier A (2012) Cardiotoxin-I: an unexpectedly potent insulinotropic agent. Chembiochem 13(12):1805–1812. doi:10.1002/cbic.201200081

    CAS  PubMed  Article  Google Scholar 

  • Nguyen TT, Folch B, Letourneau M, Truong NH, Doucet N, Fournier A, Chatenet D (2014) Design of a truncated cardiotoxin-I analogue with potent insulinotropic activity. J Med Chem 57(6):2623–2633. doi:10.1021/jm401904q

    CAS  PubMed  Article  Google Scholar 

  • Oguiura N, Boni-Mitake M, Affonso R, Zhang G (2011) In vitro antibacterial and hemolytic activities of crotamine, a small basic myotoxin from rattlesnake Crotalus durissus. J Antibiot (Tokyo) 64(4):327–331. doi:10.1038/ja.2011.10

    CAS  Article  Google Scholar 

  • Okubo BM, Silva ON, Migliolo L, Gomes DG, Porto WF, Batista CL, Ramos CS, Holanda HH, Dias SC, Franco OL, Moreno SE (2012) Evaluation of an antimicrobial L-amino acid oxidase and peptide derivatives from Bothropoides mattogrosensis pitviper venom. PLoS One 7(3):e33639. doi:10.1371/journal.pone.0033639

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Ollert M, Blank S (2015) Anaphylaxis to insect venom allergens: role of molecular diagnostics. Curr Allergy Asthma Rep 15(5):26. doi:10.1007/s11882-015-0527-z

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  • Oyama E, Takahashi H (2015) Purification and characterization of two platelet-aggregation inhibitors, named angustatin and H-toxin TA(2), from the venom of Dendroaspis angusticeps. Toxicon 93:61–67. doi:10.1016/j.toxicon.2014.11.002

    CAS  PubMed  Article  Google Scholar 

  • Pal SK, Gomes A, Dasgupta SC, Gomes A (2002) Snake venom as therapeutic agents: from toxin to drug development. Indian J Exp Biol 40(12):1353–1358

    CAS  PubMed  Google Scholar 

  • Peng SS, Kumar TK, Jayaraman G, Chang CC, Yu C (1997) Solution structure of toxin b, a long neurotoxin from the venom of the king cobra (Ophiophagus hannah). J Biol Chem 272(12):7817–7823

    CAS  PubMed  Article  Google Scholar 

  • Petrova SD, Atanasov VN, Balashev K (2012) Vipoxin and its components: structure-function relationship. Adv Protein Chem Struct Biol 87:117–153. doi:10.1016/B978-0-12-398312-1.00005-6

    CAS  PubMed  Article  Google Scholar 

  • Pizzo SV, Schwartz ML, Hill RL, McKee PA (1972) Mechanism of ancrod anticoagulation. A direct proteolytic effect on fibrin. J Clin Invest 51(11):2841–2850. doi:10.1172/JCI107107

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Pu XC, Wong PT, Gopalakrishnakone P (1995) A novel analgesic toxin (hannalgesin) from the venom of king cobra (Ophiophagus hannah). Toxicon 33(11):1425–1431

    CAS  PubMed  Article  Google Scholar 

  • Rajendra W, Armugam A, Jeyaseelan K (2004) Toxins in anti-nociception and anti-inflammation. Toxicon 44(1):1–17. doi:10.1016/j.toxicon.2004.04.014

    CAS  PubMed  Article  Google Scholar 

  • Reid PF (2007) Alpha-cobratoxin as a possible therapy for multiple sclerosis: a review of the literature leading to its development for this application. Crit Rev Immunol 27(4):291–302

    CAS  PubMed  Article  Google Scholar 

  • Rioli V, Prezoto BC, Konno K, Melo RL, Klitzke CF, Ferro ES, Ferreira-Lopes M, Camargo AC, Portaro FC (2008) A novel bradykinin potentiating peptide isolated from Bothrops jararacussu venom using catallytically inactive oligopeptidase EP24.15. FEBS J 275(10):2442–2454. doi:10.1111/j.1742-4658.2008.06389.x

    CAS  PubMed  Article  Google Scholar 

  • Rosing J, Tans G (1992) Structural and functional properties of snake venom prothrombin activators. Toxicon 30(12):1515–1527

    CAS  PubMed  Article  Google Scholar 

  • Russo P, Catassi A, Cesario A, Servent D (2006) Development of novel therapeutic strategies for lung cancer: targeting the cholinergic system. Curr Med Chem 13(29):3493–3512

    CAS  PubMed  Article  Google Scholar 

  • Salinas M, Besson T, Delettre Q, Diochot S, Boulakirba S, Douguet D, Lingueglia E (2014) Binding site and inhibitory mechanism of the mambalgin-2 pain-relieving peptide on acid-sensing ion channel 1a. J Biol Chem 289(19):13363–13373. doi:10.1074/jbc.M114.561076

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Samy RP, Stiles BG, Chinnathambi A, Zayed ME, Alharbi SA, Franco OL, Rowan EG, Kumar AP, Lim LH, Sethi G (2015) Viperatoxin-II: a novel viper venom protein as an effective bactericidal agent. FEBS Open Bio 5:928–941. doi:10.1016/j.fob.2015.10.004

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Santos-Filho NA, Silveira LB, Oliveira CZ, Bernardes CP, Menaldo DL, Fuly AL, Arantes EC, Sampaio SV, Mamede CC, Beletti ME, de Oliveira F, Soares AM (2008) A new acidic myotoxic, anti-platelet and prostaglandin I2 inductor phospholipase A2 isolated from Bothrops moojeni snake venom. Toxicon 52(8):908–917. doi:10.1016/j.toxicon.2008.08.020

    CAS  PubMed  Article  Google Scholar 

  • Schroeder CI, Rash LD, Vila-Farres X, Rosengren KJ, Mobli M, King GF, Alewood PF, Craik DJ, Durek T (2013) Chemical synthesis, 3D structure, and ASIC binding site of the toxin mambalgin-2. Angew Chem Int Ed Engl 53(4):1017–1020. doi:10.1002/anie.201308898

    PubMed  Article  CAS  Google Scholar 

  • Selistre-de-Araujo HS, Pontes CL, Montenegro CF, Martin AC (2010) Snake venom disintegrins and cell migration. Toxins (Basel) 2(11):2606–2621. doi:10.3390/toxins2112606

    CAS  Article  Google Scholar 

  • Servent D, Fruchart-Gaillard C (2009) Muscarinic toxins: tools for the study of the pharmacological and functional properties of muscarinic receptors. J Neurochem 109(5):1193–1202. doi:10.1111/j.1471-4159.2009.06092.x

    CAS  PubMed  Article  Google Scholar 

  • Servent D, Blanchet G, Mourier G, Marquer C, Marcon E, Fruchart-Gaillard C (2011) Muscarinic toxins. Toxicon 58(6–7):455–463. doi:10.1016/j.toxicon.2011.08.004

    CAS  PubMed  Article  Google Scholar 

  • Shenoy KV, Baliga M, Mahajan S, VR K (2015) The effects of topical hemocoagulase solution on the healing process of post-extraction wounds: a split mouth design. J Maxillofac Oral Surg 14(3):586–593. doi:10.1007/s12663-014-0700-2700

    PubMed  Article  Google Scholar 

  • Shiu JH, Chen CY, Chang LS, Chen YC, Lo YH, Liu YC, Chuang WJ (2004) Solution structure of gamma-bungarotoxin: the functional significance of amino acid residues flanking the RGD motif in integrin binding. Proteins 57(4):839–849. doi:10.1002/prot.20269

    CAS  PubMed  Article  Google Scholar 

  • Smith CG, Vane JR (2003) The discovery of captopril. FASEB J 17(8):788–789. doi:10.1096/fj.03-0093life17/8/788

    CAS  PubMed  Article  Google Scholar 

  • Son DJ, Park MH, Chae SJ, Moon SO, Lee JW, Song HS, Moon DC, Kang SS, Kwon YE, Hong JT (2007) Inhibitory effect of snake venom toxin from Vipera lebetina turanica on hormone-refractory human prostate cancer cell growth: induction of apoptosis through inactivation of nuclear factor kappaB. Mol Cancer Ther 6(2):675–683. doi:10.1158/1535-7163.MCT-06-0328

    CAS  PubMed  Article  Google Scholar 

  • Stephen PM (2009) The field of reptile toxinology handbook of venoms and toxins of reptiles. CRC. C1—Snakes, lizards, and their venoms, pp. 3–23

  • Teixeira-Ferreira A, Alves EW (2007) Characterization of a novel ADPase in Bothrops jararaca snake venom involved in nucleotide hydrolysis. Protein Pept Lett 14(4):395–402

    CAS  PubMed  Article  Google Scholar 

  • Tsai PC, Chu CL, Chiu CC, Chang LS, Lin SR (2013) Inhibition of Src activation with cardiotoxin III blocks migration and invasion of MDA-MB-231 cells. Toxicon 74:56–67. doi:10.1016/j.toxicon.2013.07.021

    CAS  PubMed  Article  Google Scholar 

  • Tsai PC, Chu CL, Chiu CC, Chang LS, Lin SR (2014) Cardiotoxin III suppresses hepatocyte growth factor-stimulated migration and invasion of MDA-MB-231 cells. Cell Biochem Funct 32(6):485–495. doi:10.1002/cbf.3041

    CAS  PubMed  Article  Google Scholar 

  • Wahby AF, el Mahdy SM, El-Mezayen HA, Salama WH, Abdel-Aty AM, Fahmy AS (2012) Egyptian horned viper Cerastes cerastes venom hyaluronidase: purification, partial characterization and evidence for its action as a spreading factor. Toxicon 60(8):1380–1389. doi:10.1016/j.toxicon.2012.08.016

    CAS  PubMed  Article  Google Scholar 

  • Wang Y-L, Kuo J-H, Lee S-C, Liu J-S, Hsieh Y-C, Shih Y-T, Chen C-J, Chiu J-J, Wu W-g (2010) Cobra CRISP functions as an inflammatory modulator via a novel Zn2+- and heparan sulfate-dependent transcriptional regulation of endothelial cell adhesion molecules. J Biol Chem 285(48):37872–37883. doi:10.1074/jbc.M110.146290

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  • Waqar M, Batool S (2015) In silico analysis of binding of neurotoxic venom ligands with acetylcholinesterase for therapeutic use in treatment of Alzheimer’s disease. J Theor Biol 372:107–117. doi:10.1016/j.jtbi.2015.02.028

    CAS  PubMed  Article  Google Scholar 

  • Wollberg Z, Shabo-Shina R, Intrator N, Bdolah A, Kochva E, Shavit G, Oron Y, Vidne BA, Gitter S (1988) A novel cardiotoxic polypeptide from the venom of Atractaspis engaddensis (burrowing asp): cardiac effects in mice and isolated rat and human heart preparations. Toxicon 26(6):525–534

    CAS  PubMed  Article  Google Scholar 

  • Wu M, Ming W, Tang Y, Zhou S, Kong T, Dong W (2013) The anticancer effect of cytotoxin 1 from Naja atra Cantor venom is mediated by a lysosomal cell death pathway involving lysosomal membrane permeabilization and cathepsin B release. Am J Chin Med 41(3):643–663. doi:10.1142/S0192415X13500456

    CAS  PubMed  Article  Google Scholar 

  • Xu JM, Song ST, Feng FY, Huang FL, Yang Y, Xie GR, Xu LG, Zhang CZ, Bruno M, Paradiso A (2006) Cobrotoxin-containing analgesic compound to treat chronic moderate to severe cancer pain: results from a randomized, double-blind, cross-over study and from an open-label study. Oncol Rep 16(5):1077–1084

    CAS  PubMed  Google Scholar 

  • Xu X, Li B, Zhu S, Rong R (2015) Hypotensive peptides from snake venoms: structure, function and mechanism. Curr Top Med Chem 15(7):658–669

    CAS  PubMed  Article  Google Scholar 

  • Yamane ES, Bizerra FC, Oliveira EB, Moreira JT, Rajabi M, Nunes GL, de Souza AO, da Silva ID, Yamane T, Karpel RL, Silva PI Jr, Hayashi MA (2013) Unraveling the antifungal activity of a South American rattlesnake toxin crotamine. Biochimie 95(2):231–240. doi:10.1016/j.biochi.2012.09.019

    CAS  PubMed  Article  Google Scholar 

  • Yamazaki Y, Morita T (2004) Structure and function of snake venom cysteine-rich secretory proteins. Toxicon 44(3):227–231. doi:10.1016/j.toxicon.2004.05.023

    CAS  PubMed  Article  Google Scholar 

  • Yang CC (1999) Cobrotoxin: structure and function. J Nat Toxins 8(2):221–233

    CAS  PubMed  Google Scholar 

  • Yang ZM, Guo Q, Ma ZR, Chen Y, Wang ZZ, Wang XM, Wang YM, Tsai IH (2015) Structures and functions of crotoxin-like heterodimers and acidic phospholipases A2 from Gloydius intermedius venom: insights into the origin of neurotoxic-type rattlesnakes. J Proteome 112:210–223. doi:10.1016/j.jprot.2014.09.009

    CAS  Article  Google Scholar 

  • Ye S, Dongyang C, Zhihong X, Dongquan S, Jin D, Jianghui Q, Jizhen Q, Pu Y, Huacheng H, Wei S, Qing J (2013) The incidence of deep venous thrombosis after arthroscopically assisted anterior cruciate ligament reconstruction. Arthroscopy 29(4):742–747. doi:10.1016/j.arthro.2013.01.017

    PubMed  Article  Google Scholar 

  • Yu C, Bhaskaran R, Chuang LC, Yang CC (1993) Solution conformation of cobrotoxin: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study. Biochemistry 32(9):2131–2136

    CAS  PubMed  Article  Google Scholar 

  • Zhang L, Cui L (2007) A cytotoxin isolated from Agkistrodon acutus snake venom induces apoptosis via Fas pathway in A549 cells. Toxicol In Vitro 21(6):1095–1103. doi:10.1016/j.tiv.2007.04.008

    CAS  PubMed  Article  Google Scholar 

  • Zhang HL, Han R, Gu ZL, Chen ZX, Chen BW, Reid PF, Raymond LN, Qin ZH (2006) A short-chain alpha-neurotoxin from Naja naja atra produces potent cholinergic-dependent analgesia. Neurosci Bull 22(2):103–109

    PubMed  Google Scholar 

  • Ziegman R, Alewood P (2015) Bioactive components in fish venoms. Toxins (Basel) 7(5):1497–1531. doi:10.3390/toxins7051497

    CAS  Article  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the award of a Health and Medical Research Fund research grant (no. 12131221) from the Food and Health Bureau; Hong Kong Special Administration Region Government research grants (no. 81201270 and 81471927) from the National Natural Science Foundation of China, People’s Republic of China; and direct grants (no. 4054049 and 4054135) from the Medicine Panel, Research Committee, The Chinese University of Hong Kong and research grant (no. JCYJ20150525092941055) from the Science and Technology Innovation Commission of Shenzhen.

Author’s contributions

YSC and RCFC were responsible for writing the review. TBN assisted in providing references for the manuscript. TBN, WYC, JHW, and LX did the final editing and proofreading of the manuscript. All authors reviewed the manuscript.

Author information

Author notes

    Affiliations

    1. State Key Laboratory of Respiratory Disease for Allergy, School of Medicine, Shenzhen University, Nanhai Ave 3688, 518060, Shenzhen, Guangdong, China

      Yau Sang Chan & Lixin Xia

    2. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

      Randy Chi Fai Cheung, Jack Ho Wong, Tzi Bun Ng & Wai Yee Chan

    Authors
    1. Yau Sang Chan
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Randy Chi Fai Cheung
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Lixin Xia
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Jack Ho Wong
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Tzi Bun Ng
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Wai Yee Chan
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Lixin Xia, Jack Ho Wong, Tzi Bun Ng or Wai Yee Chan.

    Ethics declarations

    Declaration

    This article does not contain any studies with human participants or animals performed by any of the authors.

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Additional information

    Yau Sang Chan and Randy Chi Fai Cheung contributed equally to this work.

    Rights and permissions

    Reprints and Permissions

    About this article

    Verify currency and authenticity via CrossMark

    Cite this article

    Chan, Y.S., Cheung, R.C.F., Xia, L. et al. Snake venom toxins: toxicity and medicinal applications. Appl Microbiol Biotechnol 100, 6165–6181 (2016). https://doi.org/10.1007/s00253-016-7610-9

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00253-016-7610-9

    Keywords

    • Snake
    • Venom
    • Toxin
    • Therapeutic