Scorpion Venom–Toxins that Aid in Drug Development: A Review

  • Arijit Ghosh
  • Rini Roy
  • Monoswini Nandi
  • Ashis MukhopadhyayEmail author


Scorpion venom components have multifaceted orientation against bacterial, viral, fungal infections and other neuronal disorders. They can modulate the ion channels (K+, Na+, Cl, Ca2+) of our body and this concept has been hypothesized in formulating pharmaceuticals. The triumphant achievement of these venom components as formulated anticancer agent in Phase I and Phase II clinical trials allure researchers to excavate beneficial venom components prohibiting DNA replication in malignant tumor cells. This review brings forth the achievements of Science and Technology in classifying the venom components as therapeutics and further application in drug product development.


Venom toxins Ion channels Arthropods Peptides Pharmaceuticals 


Compliance with Ethical Standards

Conflict of interest

Authors disclose no conflict of interest.


  1. Ahluwalia S, Shah N (2014) Animal venom for treating breast cancer. Int J Pharm Pharm Sci 6(9):24–30Google Scholar
  2. Bancroft D (2016) Venoms and the nervous system. Big Picture.
  3. Bawaskar HS, Bawaskar PH (2012) Scorpion sting: update. J Assoc Physicians India 60:46–55Google Scholar
  4. Bennett PB, Guthrie HRE (2003) Trends in ion channel drug discovery: advances in screening technologies. Trends Biotechnol 21(12):563–569CrossRefGoogle Scholar
  5. Bergeron ZL, Bingham JP (2012) Scorpion toxins specific for potassium (K+) channels: a historical overview of peptide bioengineering. Toxins 4(11):1082–1119CrossRefGoogle Scholar
  6. Burke B (2015) How scorpion venom could yield new cancer treatment.
  7. Camargo AC, Ianzer D, Guerreiro JR, Serrano SM (2012) Bradykinin-potentiating peptides: beyond captopril. Toxicon 59(4):516–523CrossRefGoogle Scholar
  8. Casewell NR, Wüster W, Vonk FJ, Harrison RA, Fry BG (2013) Complex cocktails: the evolutionary novelty of venoms. Trends Ecol Evol 28(4):219–229CrossRefGoogle Scholar
  9. Cassini-Vieira P, Felipetto M, Prado LB, Verano-Braga T, Andrade SP, Santos RAS, Teixeira MM, de Lima ME, Pimenta AMC, Barcelos LS (2017) Ts14 from Tityus serrulatus boosts angiogenesis and attenuates inflammation and collagen deposition in sponge-induced granulation tissue in mice. Peptides 98:63–69CrossRefGoogle Scholar
  10. Catterall WA (1976) Purification of a toxic protein from scorpion venom which activates the action potential Na+ ionophore. J Biol Chem 251(18):5528–5536Google Scholar
  11. Catterall WA (2000) From ionic currents to molecular mechanisms: the structure and function of voltagegated sodium channels. Neuron 26(1):13–25CrossRefGoogle Scholar
  12. Chaisakul J, Hodgson WC, Kuruppu S, Prasongsook N (2016) Effects of animal venoms and toxins on hallmarks of cancer. J Cancer 7(11):1571–1578CrossRefGoogle Scholar
  13. Chandy KG, Wulff H, Beeton C, Pennington M, Gutman GA, Cahalan MD (2004) K+ channels as targets for specific immunomodulation. Trends Pharmacol Sci 25(5):280–289CrossRefGoogle Scholar
  14. Chen Y, Cao L, Zhong M, Zhang Y, Han C, Li Q, Yang J, Zhou D, Shi W, He B, Liu F, Yu J, Sun Y, Cao Y, Li Y, Li W, Guo D, Cao Z, Yan H (2012) Anti-HIV-1 activity of a new scorpion venom peptide derivative Kn2-7. PLoS ONE 7(4):e34947CrossRefGoogle Scholar
  15. Cremonez CM, Maiti M, Peigneur S, Cassoli JS, Dutra AAA, Waelkens E, Lescrinier E, Herdewijn P, Elena de Lima M, Pimenta AMC, Arantes EC, Tytgat J (2016) Structural and functional elucidation of peptide Ts11 shows evidence of a novel subfamily of scorpion venom toxins. Toxins 8(10):288–301CrossRefGoogle Scholar
  16. D’Suze G, Rosales A, Salazar V, Sevcik C (2010) Apoptogenic peptides from Tityus discrepans scorpion venom acting against the SKBR3 breast cancer cell line. Toxicon 56(8):1497–1505CrossRefGoogle Scholar
  17. Daniele-Silva A, Machado RJ, Monteiro NK, Estrela AB, Santos EC, Carvalho E, AraújoJúnior RF, Melo-Silveira RF, Rocha HA, Silva-Júnior AA, Fernandes-Pedrosa MF (2016) Stigmurin and TsAP-2 from Tityus stigmurus scorpion venom: assessment of structure and therapeutic potential in experimental sepsis. Toxicon 121:10–21CrossRefGoogle Scholar
  18. Dardevet L, Rani D, Abd El Aziz T, Bazin I, Sabatier JM, Fadl M, Brambilla E, De Waard M (2015) Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion. Toxins (Basel) 7(4):1079–1101CrossRefGoogle Scholar
  19. Das Gupta S, Debnath A, Saha A, Giri B, Tripathi G, Vedasiromoni JR, Gomes A, Gomes A (2007) Indian black scorpion (Heterometrus bengalensis Koch) venom induced antiproliferative and apoptogenic activity against human leukemic cell lines U937 and K562. Leuk Res 31(6):817–825CrossRefGoogle Scholar
  20. Di Lorenzo L, Palmieri C, Cusano A, Foti C (2012) Cancer pain management with a venom of blue scorpion endemic in Cuba, called Rhopalurus junceus “Escozul”. Open Cancer J 5:1–2CrossRefGoogle Scholar
  21. Díaz-García A, Morier-Díaz L, Frión-Herrera Y, Rodríguez-Sánchez H, Caballero-Lorenzo Y, Mendoza-Llanes D, Riquenes-Garlobo Y, Fraga-Castro JA (2013) In vitro anticancer effect of venom from Cuban scorpion Rhopalurus junceus against a panel of human cancer cell lines. J Venom Res 4:5–12Google Scholar
  22. Díaz-García A, Ruiz-Fuentes JL, Rodríguez-Sánchez H, Castro JAF (2017) Rhopalurus junceus scorpion venom induces apoptosis in the triple negative human breast cancer cell line MDA-MB-231. J Venom Res 8:9–13Google Scholar
  23. Dutertre S, Lewis RJ (2010) Use of venom peptides to probe ion channel structure and function. J Biol Chem 285(18):13315–13320CrossRefGoogle Scholar
  24. El-Bitar AMH, Sarhan MMH, Aoki C, Takahara Y, Komoto M, Deng L, Moustafa MA, Hotta H (2015) Virocidal activity of Egyptian scorpion venoms against hepatitis C virus. Virol J 12:47CrossRefGoogle Scholar
  25. Escoubas P, King GF (2009) Venomics as a drug discovery platform. Expert Rev Proteomics 6(3):221–224CrossRefGoogle Scholar
  26. Gao B, Sherman P, Luo L, Bowie J, Zhu S (2009) Structural and functional characterization of two genetically related meucin peptides highlights evolutionary divergence and convergence in antimicrobial peptides. FASEB J 23(4):1230–1245CrossRefGoogle Scholar
  27. Gao B, Xu J, Rodriguez Mdel C, Lanz-Mendoza H, Hernández-Rivas R, Du W, Zhu S (2010) Characterization of two linear cationic antimalarial peptides in the scorpion Mesobuthus eupeus. Biochimie 92(4):350–359CrossRefGoogle Scholar
  28. Gomes A, Bhattacharya P, Mishra R, Biswas AK, Dasgupta SC, Giri B (2010) Anticancer potential of animal venom and toxins. Indian J Exp Biol 48(2):93–103Google Scholar
  29. Gomes da Mata ÉC, Mourão CBF, Rangel M, Schwartz EF (2017) Antiviral activity of animal venom peptides and related compounds. J Venom Anim Toxins Incl Trop Dis 23:3CrossRefGoogle Scholar
  30. Goudarzi HR, Nazari A, Noofeli M, Samiani M (2017) Bioassay of derived components from venom of Iranian medically important scorpions to identify the bradykinin potentiating factors.
  31. Gwee MC, Nirthanan S, Khoo HE, Gopalakrishnakone P, Kini RM, Cheah LS (2002) Autonomic effects of some scorpion venoms and toxins. Clin Exp Pharmacol Physiol 29(9):795–801CrossRefGoogle Scholar
  32. Harvey AL (2014) Toxins and drug discovery. Toxicon 92:193–200CrossRefGoogle Scholar
  33. Heinen TE, da Veiga AB (2011) Arthropod venoms and cancer. Toxicon 57(4):497–511CrossRefGoogle Scholar
  34. Henney NC (2015) Glenn F. King: venoms to drugs: venom as a source for the development of human therapeutics. Chromatographia 78(23–24):1507–1508CrossRefGoogle Scholar
  35. Hmed BN, Serria HT, Mounir ZK (2013) Scorpion peptides: potential use for new drug development. J Toxicol 2013:958797CrossRefGoogle Scholar
  36. Inceoglu B, Lango J, Jing J, Chen L, Doymaz F, Pessah IN, Hammock BD (2003) One scorpion, two venoms: prevenom of Parabuthus transvaalicus acts as an alternative type of venom with distinct mechanism of action. Proc Natl Acad Sci USA 100(3):922–927CrossRefGoogle Scholar
  37. Investigación y Desarrollo (2015) Scorpion venom is toxic to cancer cells. ScienceDaily. Retrieved 8 December 2017
  38. Israel MR, Tay B, Deuis JR, Vetter I (2017) Sodium channels and venom peptide pharmacology. Adv Pharmacol 79:67–116CrossRefGoogle Scholar
  39. Kaczorowski GJ, McManus OB, Priest BT, Garcia ML (2008) Ion channels as drug targets: the next GPCRs. J Gen Physiol 131(5):399–405CrossRefGoogle Scholar
  40. Kastin AJ (2006) Handbook of biologically active peptides, Chapter 51, 1st edn. Academic Press, Boston, p 339Google Scholar
  41. Krishnamurthy KR (2000) The scorpion envenoming syndrome: a different perspective. The physiological basis of the role of insulin in scorpion envenoming. J Venom Anim Toxins 6(1):4–51CrossRefGoogle Scholar
  42. Liu YF, Ma RL, Wang SL, Duan ZY, Zhang JH, Wu LJ, Wu CF (2003) Expression of an antitumor–analgesic peptide from the venom of Chinese scorpion Buthus martensii karsch in Escherichia coli. Protein Expr Purif 27(2):253–258CrossRefGoogle Scholar
  43. Luna-Ramírez K, Quintero-Hernández V, Juárez-González VR, Possani LD (2015) Whole transcriptome of the venom gland from Urodacus yaschenkoi scorpion. PLoS ONE 10(5):e0127883CrossRefGoogle Scholar
  44. Luna-Ramírez K, Jiménez-Vargas JM, Possani LD (2016) Scorpine-like peptides. Single Cell Biol 5:2Google Scholar
  45. Machado RJ, Estrela AB, Nascimento AK, Melo MM, Torres-Rêgo M, Lima EO, Rocha HA, Carvalho E, Silva-Junior AA, Fernandes-Pedrosa MF (2016) Characterization of TistH, a multifunctional peptide from the scorpion Tityus stigmurus: structure, cytotoxicity and antimicrobial activity. Toxicon 119:362–370CrossRefGoogle Scholar
  46. Mishal R, Tahir HM, Zafar K, Arshad M (2013) Anticancerous applications of scorpion venom. Int J Biol Pharm Res 4(5):356–360Google Scholar
  47. Monteith GR, Davis FM, Roberts-Thomson SJ (2012) Calcium channels and pumps in cancer: changes and consequences. J Biol Chem 287(38):31666–31673CrossRefGoogle Scholar
  48. Niemeyer BA, Mery L, Zawar C, Suckow A, Monje F, Pardo LA, Stuhmer W, Flockerzi V, Hoth M (2001) Ion channels in health and disease. 83rd Boehringer Ingelheim Fonds International Titisee Conference. EMBO Rep 2(7):568–573CrossRefGoogle Scholar
  49. Ning YN, Zhang WD, Wu LC (2012) Study on the mechanism of polypeptide extract from scorpion venom to promote the restraint of cyclophosphamide on Lewis lung cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi 32(4):537–542Google Scholar
  50. Ortiz E, Gurrola GB, Schwartz EF, Possani LD (2014) Scorpion venom components as potential candidates for drug development. Toxicon 93:125–135CrossRefGoogle Scholar
  51. Oukkache N, Chgoury F, Lalaoui M, Cano AA, Ghalim N (2013) Comparison between two methods of scorpion venom milking in Morocco. J Venom Anim Toxins Incl Trop Dis 19(1):5CrossRefGoogle Scholar
  52. Petricevich VL (2010) Scorpion venom and the inflammatory response. Mediators Inflamm 2010:903295CrossRefGoogle Scholar
  53. Petricevich VL, Navarro LB, Possani LD (2013) Therapeutic use of scorpion venom. Mol Asp Inflamm 9:209–231Google Scholar
  54. Plummer L (2017) Robots are milking scorpions for venom that can be used in cancer research.
  55. Podnar O (2015) Blue scorpion venom drug—Vidatox—a proven help against many types of carcinoma.
  56. Possani LD, Merino E, Corona M, Bolivar F, Becerril B (2000) Peptides and genes coding for scorpion toxins that affect ion-channels. Biochimie 82(9–10):861–868CrossRefGoogle Scholar
  57. Quintero-Hernándeza V, Jiménez-Vargasa JM, Gurrolaa GB, Valdivia HHF, Possani LD (2013) Scorpion venom components that affect ion-channels function. Toxicon 76:328–342CrossRefGoogle Scholar
  58. Rapini RP, Bolognia JL, Jorizzo JL (2007) Dermatology: 2-volume set. Mosby, St. Louis, p 1315Google Scholar
  59. Remijsen Q, Verdonck F, Willems J (2010) Parabutoporin, a cationic amphipathic peptide from scorpion venom: much more than an antibiotic. Toxicon 55(2–3):180–185CrossRefGoogle Scholar
  60. 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 catalytically inactive oligopeptidase EP24.15. FEBS J 275(10):2442–2454CrossRefGoogle Scholar
  61. Rocha e Silva M, Beraldo WT, Rosenfeld G (1949) Bradykinin, a hypotensive and smooth muscle stimulating factor released from plasma globulin by snake venoms and by trypsin. Am J Physiol Leg 156(2):261–273CrossRefGoogle Scholar
  62. Smith JJ, Jones A, Alewood PF (2012) Mass landscapes of seven scorpion species: the first analyses of Australian species with 1,5-DAN matrix. J Venom Res 3:7–14Google Scholar
  63. Stevens M, Peigneur S, Tytgat J (2011) Neurotoxins and their binding areas on voltage-gated sodium channels. Front Pharmacol 2:71CrossRefGoogle Scholar
  64. Sun C, Fang C, Stephen Z, Veiseh O, Hansen S, Lee D, Ellenbogen RG, Olson J, Zhang M (2008) Tumortargeted drug delivery and MRI contrast enhancement by chlorotoxin conjugated iron oxide nanoparticles. Nanomed 3:495CrossRefGoogle Scholar
  65. Takahashi H (2014) The selection that nobody talks about.
  66. Utkin YN (2015) Animal venom studies: current benefits and future developments. World J Biol Chem 6(2):28–33CrossRefGoogle Scholar
  67. Verano-Braga T, Rocha-Resende C, Silva DM, Ianzer D, Martin-Eauclaire MF, Bougis PE, de Lima ME, Santos RA, Pimenta AM (2008) Tityus serrulatus Hypotensins: a new family of peptides from scorpion venom. Biochem Biophys Res Commun 371(3):515–520CrossRefGoogle Scholar
  68. Villalonga N, Ferreres JC, Argilés JM, Condom E, Felipe A (2007) Potassium channels are a new target field in anticancer drug design. Recent Pat Anticancer Drug Discov 2(3):212–223CrossRefGoogle Scholar
  69. Willems J, Moerman L, Bosteels S, Bruyneel E, Ryniers F, Verdonck F (2004) Parabutoporin—an antibiotic peptide from scorpion venom—can both induce activation and inhibition of granulocyte cell functions. Peptides 25(7):1079–1084CrossRefGoogle Scholar
  70. Williams DJ, Gutiérrez JM, Calvete JJ, Wüster W, Ratanabanangkoon K, Paiva O et al (2011) Ending the drought: new strategies for improving the flow of affordable, effective antivenoms in Asia and Africa. J Proteomics 74(9):1735–1767CrossRefGoogle Scholar
  71. Yan R, Zhao Z, He Y, Wu L, Cai D, Hong W, Wu Y, Cao Z, Zheng C, Li W (2011) A new natural α-helical peptide from the venom of the scorpion Heterometrus petersii kills HCV. Peptides 32(1):11–19CrossRefGoogle Scholar
  72. Young HS, Herbette LG, Skita V (2003) α-Bungarotoxin binding to acetylcholine receptor membranes studied by low angle X-ray diffraction. Biophys J 85(2):943–953CrossRefGoogle Scholar
  73. Zabihollahi R, PooshangBagheri K, Keshavarz Z, Motevalli F, Bahramali G, Siadat SD, Momen SB, Shahbazzadeh D, Aghasadeghi MR (2016) Venom components of Iranian scorpion Hemiscorpius lepturus inhibit the growth and replication of human immunodeficiency virus 1 (HIV-1). Iran Biomed J 20(5):259–265Google Scholar
  74. Zargan J, Umar S, Sajad M, Naime M, Ali S, Khan HA (2011) Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of mitochondria and reduces S-phase population in human breast cancer cells (MCF-7). Toxicol In Vitro 25(8):1748–1756CrossRefGoogle Scholar
  75. Zeng XC, Wang SX, Zhu Y, Zhu SY, Li WX (2004) Identification and functional characterization of novel scorpion venom peptides with no disulfide bridge from Buthus martensii Karsch. Peptides 25(2):143–150CrossRefGoogle Scholar
  76. Zeng XC, Corzo G, Hahin R (2005) Scorpion venom peptides without disulfide bridges. IUBMB Life 57(1):13–21CrossRefGoogle Scholar
  77. Zeng XC, Zhou L, Shi W, Luo X, Zhang L, Nie Y, Wang J, Wu S, Cao B, Cao H (2013) Three new antimicrobial peptides from the scorpion Pandinus imperator. Peptides 45:28–34CrossRefGoogle Scholar
  78. Zhang YY, Wu LC, Wang ZP, Wang ZX, Jia Q, Jiang GS, Zhang WD (2009) Anti-proliferation effect of polypeptide extracted from scorpion venom on human prostate cancer cells in vitro. J Clin Med Res 1(1):24–31Google Scholar
  79. Zhang F, Xu X, Li T, Liu Z (2013) Shellfish toxins targeting voltage-gated sodium channels. Mar Drugs 11(12):4698–4723CrossRefGoogle Scholar
  80. Zhang C, He X, Gu Y, Zhou H, Cao J, Gao Q (2014) Recombinant scorpine produced using SUMO fusion partner in Escherichia coli has the activities against clinically isolated bacteria and inhibits the Plasmodium falciparum parasitemia in vitro. PLoS ONE 9(7):e103456CrossRefGoogle Scholar
  81. Zhu S, Gao B (2006) Molecular characterization of a new scorpion venom lipolysis activating peptide: evidence for disulfide bridge-mediated functional switch of peptides. FEBS Lett 580(30):6825–6836CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Molecular BiologyNetaji Subhas Chandra Bose Cancer Research InstituteKolkataIndia
  2. 2.Department of Molecular Biology and BiotechnologyKalyani UniversityKalyaniIndia
  3. 3.Department of Hemato-OncologyNetaji Subhas Chandra Bose Cancer Research InstituteKolkataIndia
  4. 4.Netaji Subhas Chandra Bose Cancer Research InstituteKolkataIndia

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