Snake Venomics, Antivenomics, and Venom Phenotyping: The Ménage à Trois of Proteomic Tools Aimed at Understanding the Biodiversity of Venoms

  • Juan J. CalveteEmail author


This review covers the application of proteomic protocols (“venomics”, “antivenomics”, and “venom phenotyping”) to studying the composition and natural history of snake venoms, and the crossreactivity of antivenoms against homologous and heterologous venoms. Toxins from the same protein family present in venoms from snakes belonging to different genera often share antigenic determinants. This circumstance offers the possibility of defining the minimal set of venoms containing the epitopes necessary to generate therapeutic broad-range polyvalent antisera. Recent work shows how the knowledge of evolutionary trends along with venom phenotyping may be used to replace the traditionally used phylogenetic hypothesis for antivenom production strategies by cladistic clustering of venoms based on proteome phenotype and immunological profile similarities.


Snake Venom Venom Gland Crude Venom Venom Protein Venom Component 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author gratefully thank the many colleagues (particularly from the Instituto Clodomiro Picado, Costa Rica) who, over the years, have provided precious venoms and antivenoms within the framework of collaborative projects and have contributed insight and suggestions. Funding for the projects described in this paper was provided by grant BFU2007-61563 from the Ministerio de Educación y Ciencia, Madrid, CRUSA-CSIC (2007CR0004), and CYTED (206AC0281). Travelling between Spain and Costa Rica was financed by Acciones Integradas, 2006CR0010 between CSIC and the University of Costa Rica (UCR).


  1. Alape-Girón, A., Sanz, L., Escolano, J., Flores-Díaz, M., Madrigal, M., Sasa, M., Calvete, J.J., 2008. Snake venomics of the lancehead pitviper Bothrops asper: geographic, individual, and ontogenetic variations. J. Proteome Res. 7, 3556–3571.PubMedCrossRefGoogle Scholar
  2. Angulo, Y., Escolano, J., Lomonte, B., Gutiérrez, J.M., Sanz, L., Calvete, J.J., 2008. Snake venomics of Central American pitvipers: clues for rationalizing the distinct envenomation profiles of Atropoides nummifer and Atropoides picadoi. J. Proteome Res. 7, 708–719.PubMedCrossRefGoogle Scholar
  3. Arce, V., Rojas, E., Ownby, C.L., Gutiérrez, J.M., 2003. Preclinical assessment of the ability of polyvalent (Crotalinae) and anticoral (Elapidae) antivenoms produced in Costa Rica to neutralize the venoms of North American snakes. Toxicon 41, 851–860.PubMedCrossRefGoogle Scholar
  4. Azofeifa-Cordero, G., Arce-Estrada, V., Flores-Diaz, M., Alape-Giron, A., 2008. Immunization with cDNA of a novel P-III type metalloproteinase from the rattlesnake Crotalus durissus durissus elicits antibodies which neutralize 69% of the hemorrhage induced by the whole venom. Toxicon 52, 302–308.PubMedCrossRefGoogle Scholar
  5. Barlow, A., Pook, C.E., Harrison, R.A., Wüster, W., 2009. Coevolution of diet and prey-specific venom activity supports the role of selection in snake venom evolution. Proc. Biol. Sci. 276, 2443–2449.PubMedCrossRefGoogle Scholar
  6. Bazaa, A., Marrakchi, N., El Ayeb, M., Sanz, L., Calvete, J.J., 2005. Snake venomics: comparative analysis of the venom proteomes of the Tunisian snakes Cerastes cerastes, Cerastes vipera and Macrovipera lebetina. Proteomics 5, 4223–4235.PubMedCrossRefGoogle Scholar
  7. Billen, B., Bosmans, F., Tytgat, J., 2008. Animal peptides targeting voltage-activated sodium channels. Curr. Pharm. Des. 14, 2492–2502.PubMedCrossRefGoogle Scholar
  8. Bogarín, G., Romero, M., Rojas, G., Lutsch, C., Casadamont, M., Lang, J., Otero, R., Gutiérrez, J.M., 1999. Neutralization, by a monospecific Bothrops lanceolatus antivenom, of toxic activities induced by homologous and heterologous Bothrops snake venoms. Toxicon 37, 551–557.PubMedCrossRefGoogle Scholar
  9. Boldrini-França, J., Rodrigues, R.S., Fonseca, F.P., Menaldo, D.L., Ferreira, F.B., Henrique-Silva, F., Soares, A.M., Hamaguchi, A., Rodrigues, V.M., Otaviano, A.R., Homsi-Brandeburgo, M.I., 2009. Crotalus durissus collilineatus venom gland transcriptome: analysis of gene expression profile. Biochimie 91, 586–595.PubMedCrossRefGoogle Scholar
  10. Bucher, B., Canonge, D., Thomas, L., Tyburn, B., Robbe-Vincent, A., Choumet, V., Bon, C., Ketterlé, J., Lang, J., 1997. Research group of snake bites in Martinique. Clinical indicators of envenoming and serum levels of venom antigens in patients bitten by Bothrops lanceolatus in Martinique. Trans. Royal Soc. Trop. Med. Hyg. 91, 186–190.CrossRefGoogle Scholar
  11. Calvete, J.J., 2009a. Venomics. J. Proteomics 72, 121–282.PubMedCrossRefGoogle Scholar
  12. Calvete, J.J., 2009b. Digging into the evolution of venomous systems and learning to twist nature to fight pathology. J. Proteomics 72, 121–126.PubMedCrossRefGoogle Scholar
  13. Calvete, J.J., Juárez, P., Sanz, L., 2007a. Snake venomics. Strategy and applications. J. Mass Spectrom. 42, 1405–1414.PubMedCrossRefGoogle Scholar
  14. Calvete, J.J., Marcinkiewicz, C., Sanz, L., 2007b. Snake venomics of Bitis gabonica gabonica. Protein family composition, subunit organization of venom toxins, and characterization of dimeric disintegrins bitisgabonin-1 and bitisgabonin-2. J. Proteome Res. 6, 326–336.PubMedCrossRefGoogle Scholar
  15. Calvete, J.J., Escolano, J., Sanz, L., 2007c. Snake venomics of Bitis species reveals large intragenus venom toxin composition variation: application to taxonomy of congeneric taxa. J. Proteome Res. 6, 2732–2745.PubMedCrossRefGoogle Scholar
  16. Calvete, J.J., Fasoli, E., Sanz, L., Boschetti, E., Righetti, P.G., 2009a. Exploring the venom proteome of the western diamondback rattlesnake, Crotalus atrox, via snake venomics and combinatorial peptide ligand library approaches. J. Proteome Res. 8, 3055–3067.PubMedCrossRefGoogle Scholar
  17. Calvete, J.J., Borges, A., Segura, A., Flores-Díaz, M., Alape-Girón, A., Gutiérrez, J.M., Diez, N., De Sousa, L., Kiriakos, D., Sánchez, E., Faks, J.G., Escolano, J., Sanz, L., 2009b. Snake venomics and antivenomics of Bothrops colombiensis, a medically important pitviper of the Bothrops atrox-asper complex endemic to Venezuela: contributing to its taxonomy and snakebite management. J. Proteomics 72, 227–240.PubMedCrossRefGoogle Scholar
  18. Calvete, J.J., Sanz, L., Cid, P., De La Torre, P., Flores-Diaz, M., Dos Santos, M.C., Borges, A., Bremo, A., Angulo, Y., Lomonte, B., Alape-Giron, A., Gutiérrez, J.M., 2010. Snake venomics of the Central American rattlesnake Crotalus simus and the South American Crotalus durissus complex points to neurotoxicity as an adaptive paedomorphic trend along Crotalus dispersal in South America. J. Proteome Res. 9, 528–544.Google Scholar
  19. Campbell, J.A., Lamar, W.W., 2004. The Venomous Reptiles of the Western Hemisphere (vols. I and II). Cornell University Press.Google Scholar
  20. Chippaux, J.P., Goyffon, M., 2008. Epidemiology of scorpionism: a global appraisal. Acta Trop. 107, 71–79.PubMedCrossRefGoogle Scholar
  21. Cidade, D.A.P., Simão, T.A., Dávila, A.M.R., Wagner, G., Junqueira-de-Azevedo, I.L.M., Ho, P.L., Bon, C., Zingali, R., Albano, R.M., 2006. Bothrops jararaca venom transcriptome: analysis of the gene expression pattern. Toxicon 48, 437–461.PubMedCrossRefGoogle Scholar
  22. Clemetson, K.J., Morita, T., Kini, R.M., 2009. Classification and nomenclature of snake venom C-type lectins and related proteins. Toxicon 54, 83.PubMedCrossRefGoogle Scholar
  23. Dart, R.C., McNally, J., 2001. Efficacy, Safety, and Use of Snake Antivenoms in the United States. Ann. Emerg. Med. 37, 181–188.PubMedCrossRefGoogle Scholar
  24. De Lima, M.E., Pimenta, A.M.C., Martin-Euclaire, M.F., Zingali, R.B., 2009. Animal Toxins: State of the Art. Perspectives in Health and Biotechnology. Editora UFMG, Belo Horizonte.Google Scholar
  25. Doley, R., Kini, R.M., 2009. Protein complexes in snake venom. Cell. Mol. Life Sci. 66, 2851–2871.PubMedCrossRefGoogle Scholar
  26. Escoubas, P., Quinton, L., Nicholson, G.M., 2008. Venomics: unravelling the complexity of animal venoms with mass spectrometry. J. Mass Spectrom. 43, 279–295.PubMedCrossRefGoogle Scholar
  27. Espino-Solís, G.P., Riaño-Umbarila, L., Becerril, B., Possani, L.D., 2009. Antidotes against venomous animals: state of the art and prospectives. J. Proteomics 72, 183–199.PubMedCrossRefGoogle Scholar
  28. Favreau, P., Menin, L., Michalet, S., Perret, F., Cheneval, O., Stöcklin, M., Bulet, P., Stöcklin, R., 2006. Mass spectrometry strategies for venom mapping and peptide sequencing from crude venoms: case applications with single arthropod specimen. Toxicon 47, 676–687.PubMedCrossRefGoogle Scholar
  29. Ferquel, E., de Haro, L., Jan, V., Guillemin, I., Jourdain, S., Teynié, A., d'Alayer, J., Choumet, V., 2007. Reappraisal of Vipera aspis venom neurotoxicity. PLoS One 21, e1194.CrossRefGoogle Scholar
  30. Fox, J.W., Serrano, S.M., 2005a. Snake toxins and hemostasis. Toxicon 45, 951–1181.CrossRefGoogle Scholar
  31. Fox, J.W., Serrano, S.M.T., 2005b. Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases. Toxicon 45, 969–985.PubMedCrossRefGoogle Scholar
  32. Fox, J.W., Serrano, S.M., 2007. Approaching the golden age of natural product pharmaceuticals from venom libraries: an overview of toxins and toxin-derivatives currently involved in therapeutic or diagnostic applications. Curr. Pharm. Des. 13, 2927–2934.PubMedCrossRefGoogle Scholar
  33. Fox, J.W., Serrano, S.M., 2009. Timeline of key events in snake venom metalloproteinase research. J. Proteomics 72, 200–209.PubMedCrossRefGoogle Scholar
  34. Fox, J.W., Ma, L., Nelson, K., Sherman, N.E., Serrano, S.M., 2006. Comparison of indirect and direct approaches using ion-trap and Fourier transform ion cyclotron resonance mass spectrometry for exploring viperid venom proteomes. Toxicon 47, 700–714.PubMedCrossRefGoogle Scholar
  35. Francischetti, I.M., My-Pham, V., Harrison, J., Garfield, M.K., Ribeiro, J.M.C., 2004. Bitis gabonica (Gaboon viper) snake venom gland: towards a catalog of full-length transcripts (cDNA) and proteins. Gene 337, 55–69.PubMedCrossRefGoogle Scholar
  36. Fry, B.G., Wickramaratna, J.C., Jones, A., Alewood, P.F., Hodgson, W.C., 2001. Species and regional variations in the effectiveness of antivenom against the in vitro neurotoxicity of death adder (Acanthophis) venoms. Toxicol. Appl. Pharmacol. 175, 140–148.PubMedCrossRefGoogle Scholar
  37. Fry, B.G., Wüster, W., 2004. Assembling an arsenal: origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences. Mol. Biol. Evol. 21, 870–873.PubMedCrossRefGoogle Scholar
  38. Fry, B.G., 2005. From genome to “venome”: molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins. Genome Res. 15, 403–420.PubMedCrossRefGoogle Scholar
  39. Fry, B.G., Scheib, H., van der Weerd, L., Young, B., McNaughtan, J., Ramjan, S.F., Vidal, N., Poelmann, R.E., Norman, J.A., 2008. Evolution of an arsenal: Structural and functional diversification of the venom system in the advanced snakes (Caenophidia). Mol. Cell Proteomics 7(2), 215–246. Epub 2007 Sep 12.PubMedGoogle Scholar
  40. Fry, B.G., Vidal, N., van der Weerd, L., Kochva, E., Renjifo, C., 2009a. Evolution and diversification of the Toxicofera reptile venom system. J. Proteomics 72, 127–136.PubMedCrossRefGoogle Scholar
  41. Fry, B.G., Roelants, K., Champagne, D.E., Scheib, H., Tyndall, J.D.A., King, G.F., Nevalainen, T.J., Norman, J.A., Lewis, R.J., Norton, R.S., Renjifo, C., Rodríguez de la Vega, R.C., 2009b. The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu. Rev. Genomics Hum. Genet. 10, 483–511.PubMedCrossRefGoogle Scholar
  42. Garstang, W., 1922. The theory of recapitulation: a critical re-statement of the biogenetic law. Linn. Soc. Jour. Zool. XXXV, 81–101.CrossRefGoogle Scholar
  43. Guércio, R.A.P., Shevchenko, A., Shevchenko, A., López-Lozano, J.L., Paba, J., Sousa, M.V., Ricart, C.A.O., 2006. Ontogenetic variations in the venom proteome of the Amazonian snake Bothrops atrox. Proteome Sci. 4, 11.PubMedCrossRefGoogle Scholar
  44. Georgieva, D., Risch, M., Kardas, A., Buck, F., von Bergen, M., Betzel, C., 2008. Comparative analysis of the venom proteomes of Vipera ammodytes ammodytes and Vipera ammodytes meridionales. J. Proteome Res. 7, 866–886.PubMedCrossRefGoogle Scholar
  45. Gibbs, H.L., Sanz, L., Calvete, J.J., 2009. Snake population venomics: proteomics-based analyses of individual variation reveals significant gene regulation effects on venom protein expression in Sistrurus rattlesnakes. J. Mol. Evol. 68, 113–125.PubMedCrossRefGoogle Scholar
  46. Gutiérrez, J.M., dos Santos, M.C., Furtado, M.F., Rojas, G., 1991. Biochemical and pharmacological similarities between the venoms of newborn Crotalus durissus durissus and adult Crotalus durissus terrificus rattlesnakes. Toxicon. 29(10), 1273–1277.PubMedCrossRefGoogle Scholar
  47. Gutiérrez, J.M., Dos Santos, M.C., Furtado, M.F., Rojas, G., 2001. Biochemical and pharmacological similarities between the venoms of newborn Crotalus durissus durissus and adult Crotalus durissus terrificus rattlesnakes. Toxicon 29, 1273–1277.CrossRefGoogle Scholar
  48. Gutiérrez, J.M., Rojas, E., Quesada, L., León, G., Núñez, J., Laing, G.D., Sasa, M., Renjifo, J.M., Nasidi, A., Warrell, D.A., Theakston, R.D.G., Rojas, G., 2005. Pan-African polyspecific antivenom produced by caprylic acid purification of horse IgG: an alternative to the antivenom crisis in Africa. Trans. Roy. Soc. Trop. Med. Hyg. 99, 468–475.PubMedCrossRefGoogle Scholar
  49. Gutiérrez, J.M., Theakston, R.D.G., Warrell, D.A., 2006. Confronting the neglected problem of snake bite envenoming: the need for a global partnership. PLoS Med. 3, e150.PubMedCrossRefGoogle Scholar
  50. Gutiérrez, J.M., Sanz, L., Escolano, J., Fernández, J., Lomonte, B., Angulo, Y., Rucavado, A., Warrell, D.A., Calvete, J.J., 2008. Snake venomic of the Lesser Antillean pit vipers Bothrops caribbaeus and Bothrops lanceolatus: correlation with toxicological activities and immunoreactivity of a heterologous antivenom. J. Proteome Res. 7, 4396–3408.PubMedCrossRefGoogle Scholar
  51. Gutiérrez, J.M., 2009. Bothrops asper: from natural history to public health. Toxicon 54, 901–1028.PubMedCrossRefGoogle Scholar
  52. Gutiérrez, J.M., León, G., 2009. Snake antivenoms, in: De Lima, M.E., Pimenta, A.M.C., Martin-Euclaire, M.F., Zingali, R.B. (Eds.), Animal Toxins: State of the Art. Perspectives in Health and Biotechnology. Editora UFMG, Belo Horizonte, Brazil, pp. 393–421.Google Scholar
  53. Gutiérrez, J.M., Lomonte, B., León, G., Alape-Girón, A., Flores-Díaz, M., Sanz, L., Angulo, Y., Calvete, J.J., 2009. Snake venomics and antivenomics: proteomic tools in the design and control of antivenoms for the treatment of snakebite envenoming. J. Proteomics 72, 227–240.PubMedCrossRefGoogle Scholar
  54. Gutiérrez, J.M., Sanz, L., Flores-Diaz, M., Figueroa, L., Madrigal, M., Herrera, M., Villalta, M., León, G., Estrada, R., Borges, A., Alape-Girón, A., Calvete, J.J., 2010. Impact of regional variation in Bothrops asper snake venom on the design of antivenoms: integrating antivenomics and neutralization approaches. J. Proteome Res. 9, 564–577.Google Scholar
  55. Harvey, A.L., Bradley, K.N., Cochran, S.A., Rowan, E.G., Pratt, J.A., Quillfeldt, J.A., Jerusalinsky, D.A., 1998. What can toxins tell us for drug discovery? Toxicon 36, 1635–1640.PubMedCrossRefGoogle Scholar
  56. Jia, Y., Cantu, B.A., Sánchez, E.E., Pérez, J.C., 2008. Complementary DNA sequencing and identification of mRNAs from the venomous gland of Agkistrodon piscivorus leucostoma. Toxicon 51, 1457–1466.PubMedCrossRefGoogle Scholar
  57. Juárez, P., Sanz, L., Calvete, J.J., 2004. Snake venomics: characterization of protein families in Sistrurus barbouri venom by cysteine mapping, N-terminal sequencing, and tandem mass spectrometry analysis. Proteomics 4, 327–328.PubMedCrossRefGoogle Scholar
  58. Juárez, P., Wagstaff, S.C., Oliver, J., Sanz, L., Harrison, R.A., Calvete, J.J., 2006. Molecular cloning of disintegrin-like transcript BA-5A from a Bitis arietans venom gland cDNA library: a putative intermediate in the evolution of the long-chain disintegrin bitistatin. J. Mol. Evol. 63, 142–152.PubMedCrossRefGoogle Scholar
  59. Juárez, P., Comas, I., González-Candelas, F., Calvete, J.J., 2008. Evolution of snake venom disintegrins by positive Darwinian selection. Mol. Biol. Evol. 25, 2391–2407.PubMedCrossRefGoogle Scholar
  60. Judge, R.K., Henry, P.J., Mirtschin, P., Jelinek, G., Wilce, J.A., 2006. Toxins not neutralized by brown snake antivenom. Toxicol. Appl. Pharmacol. 213, 117–125.PubMedCrossRefGoogle Scholar
  61. Junqueira-de-Azevedo, I.L., Ho, P.L., 2002. A survey of gene expression and diversity in the venom glands of the pitviper snake Bothrops insularis through the generation of expressed sequence tags (ESTs). Gene 299, 279–291.CrossRefGoogle Scholar
  62. Junqueira-de-Azevedo, I.L.M., Ching, A.T.C., Carvalho, E., Faria, F., Nishiyama M.Y., Jr., Ho, P.L., Diniz, M.R.V., 2006. Lachesis muta (Viperidae) cDNAs reveal diverging pitviper molecules and scaffolds typical of cobra (Elapidae) venoms: implications in snake toxin repertoire evolution. Genetics 173, 877–889.PubMedCrossRefGoogle Scholar
  63. Junqueira de Azevedo, I.L.M., Diniz, M.R.V., Ho, P.L., 2009. Venom gland transcriptomic analysis, in: De Lima, M.E., Pimenta, A.M.C., Martin-Euclaire, M.F., Zingali, R.B. (Eds.), Animal Toxins: State of the Art. Perspectives in Health and Biotechnology. Editora UFMG, Belo Horizonte, Brazil, pp. 693–713.Google Scholar
  64. Kashima, S., Roberto, P.G., Soares, A.M., Astolfi-Filho, S., Pereira, J.O., Giuliati, S., Faria M., Jr., Xavier, M.A.S., Fontes, M.R.M., Giglio, J.R., Franca, S.C.., 2004. Analysis of Bothrops jararacussu venomous gland transcriptome focusing on structural and functional aspect: I-gene expression profile of highly expressed phospholipases A2. Biochimie 86, 211–219.PubMedCrossRefGoogle Scholar
  65. Kasturiratne, A., Wickremasinghe, A.R., de Silva, N., Gunawardena, N.K., Pathmeswaran, A., Premaratna, R., Savioli, L., Lalloo, D.G., de Silva, H.J., 2008. The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med. 5, e218.PubMedCrossRefGoogle Scholar
  66. Kem, W.R., Turk T., 2009. Cnidarian toxins and venoms. Toxicon 54, 1029–1214.PubMedCrossRefGoogle Scholar
  67. Koh, D.C.I., Armugam, A., Jeyaseelan, K., 2007. Snake venom components and their applications in biomedicine. Cell. Mol. Life Sci. 63, 3030–3041.CrossRefGoogle Scholar
  68. Kulkeaw K, Chaicump W, Sakolvaree Y, Tongtawe P, Tapchaisri P., 2007. Proteome and immunome of the venom of the Thai cobra, Naja kaouthia. Toxicon 49, 1026–1041.PubMedCrossRefGoogle Scholar
  69. Liang, S., 2008. Proteome and peptidome profiling of spider venoms. Expert Rev. Proteomics 5, 731–746.PubMedCrossRefGoogle Scholar
  70. Lomonte, B., Escolano, J., Fernández, J., Sanz, L., Angulo, Y., Gutiérrez, J.M., Calvete, J.J., 2008. Snake venomics and antivenomics of the arboreal neotopical pitvipers Bothriechis lateralis and Bothriehis schlegelii. J. Proteome Res. 7, 2445–2457.PubMedCrossRefGoogle Scholar
  71. Mackessy, S.P., 2008. Venom composition in rattlesnakes: trends and biological significance, in: Hayes, W.K., Beaman, K.R., Cardwell, M.D., Bush, S.P. (Eds.), The Biology of Rattlesnakes. Loma Linda University Press, Loma Linda, CA, pp. 495–510.Google Scholar
  72. Mackessy, S.P., 2009. Handbook of Venoms and Toxins of Reptiles. CRC Press, Taylor & Francis, Boca Ratón, FL, pp. 1–507.CrossRefGoogle Scholar
  73. Nei, M., Gu, X., Sitnikova, T., 1997. Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc. Natl. Acad. Sci. U.S.A. 94, 7799–7806.PubMedCrossRefGoogle Scholar
  74. Neiva, M., Arraes, F.B., de Souza, J.V., Rádis-Baptista, G., Prieto da Silva, A.R., Walter, M.E., Brigido, M. de M., Yamane, T., López-Lozano, J.L., Astolfi-Filho, S., 2009. Transcriptome analysis of the Amazonian viper Bothrops atrox venom gland using expressed sequence tags (ESTs). Toxicon 53, 427–436.PubMedCrossRefGoogle Scholar
  75. Norton, R.S., Olivera, B.M., 2006. Conotoxins down under. Toxicon 48, 789–798.Google Scholar
  76. Núñez, V., Cid, P., Sanz, L., De La Torre, P., Angulo, Y., Lomonte, B., Gutiérrez, J.M., Calvete, J.J., 2009. Snake venomics and antivenomics of Bothrops atrox venoms from Colombia and the Amazon regions of Brazil, Perú and Ecuador suggest the occurrence of geographic variation of venom phenotype by a trend towards paedomorphism. J. Proteomics 73, 57–78.PubMedCrossRefGoogle Scholar
  77. Ohno, M., Menez, R., Ogawa, T., Danse, J.M., Shimohigashi, Y., Fromen, C., Ducancel, F., Zinn-Justin, S., Le Du, M.H., Boulain, J.C., Tamiya, T., Menez, A., 1998. Molecular evolution of snake toxins: is the functional diversity of snake toxins associated with a mechanism of accelerated evolution? Prog. Nucleic Acid Res. Mol. Biol. 59, 307–364.CrossRefGoogle Scholar
  78. Olivera, B.M., 2006. Conus peptides: biodiversity-based discovery and exogenomics. J. Biol. Chem. 281, 31173–31177.PubMedCrossRefGoogle Scholar
  79. Olivera, B.M., Bulaj, G., Garrett, J., Terlau, H., Imperial, J., 2009. Peptide toxins from the venoms of cone snails and other toxoglossan gastropods, in: De Lima, M.E., Pimenta, A.M.C., Martin-Euclaire, M.F., Zingali, R.B. (Eds.), Animal Toxins: State of the Art. Perspectives in Health and Biotechnology. Editora UFMG, Belo Horizonte, Brazil, pp. 25–48.Google Scholar
  80. Pahari, S., Mackessy, S.P., Kini, R.M., 2007. Rattlesnake (Sistrurus catenatus edwardsii): towards an understanding of venom composition among advanced snakes (Superfamily Colubroidea). BMC Mol. Biol. 8, 115.PubMedCrossRefGoogle Scholar
  81. Qinghua, L., Xiaowei, Z., Wei, Y., Chenji, L., Yijun, H., Pengxin, Q., Xingwen, S., Songnian, H., Guangmei, Y., 2006. A catalog for transcripts in the venom gland of the Agkistrodon acutus: identification of the toxins potentially involved in coagulopathy. Biochem. Biophys. Res. Commun. 341, 522–531.PubMedCrossRefGoogle Scholar
  82. Richardson, W.H., Tanen, D.A., Tong, T.C., Betten, D.P., Carstairs, S.D., Williams, S.R., Cantrell, F.L., Clark, R.F., 2005. Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the neutralization of South American Viperidae venoms in a murine model. Ann. Emerg. Med. 45, 595–602.PubMedCrossRefGoogle Scholar
  83. Risch, M., Georgieva, D., von Bergen, M., Jehmlich, N., Genov, N., Arni, R.K., Betzel, C., 2009. Snake Venomics of the Siamese Russell's Viper (Daboia russelli siamensis) – relation to pharmacological activities. J. Proteomics 72, 256–269.PubMedCrossRefGoogle Scholar
  84. Sánchez, E.E., Ramírez, M.S., Galán, J.A., López, G., Rodríguez-Acosta, A, Pérez, J.C., 2003a. Cross reactivity of three antivenoms against North American snake venoms. Toxicon 41, 315–320.PubMedCrossRefGoogle Scholar
  85. Sánchez, E.E., Galán, J.A., Rodríguez-Acosta, A, Chase, P., Pérez, J.C., 2003b. Cross reactivity of three antivenoms against North American snake venoms. Toxicon 41, 357–365.PubMedCrossRefGoogle Scholar
  86. Sanz, L., Gibbs, H.L., Mackessy, S.P., Calvete, J.J., 2006. Venom proteomes of closely related Sistrurus rattlesnakes with divergent diets. J. Proteome Res. 5, 2098–2112.PubMedCrossRefGoogle Scholar
  87. Sanz, L., Escolano, J., Ferretti, M., Biscoglio, M.J., Rivera, E., Crescenti, E.J., Angulo, Y., Lomonte, B., Gutiérrez, J.M., Calvete, J.J., 2008a. Snake venomics of the South and Central American Bushmasters. Comparison of the toxin composition of Lachesis muta gathered from proteomic versus transcriptomic analysis. J. Proteomics 71, 46–60.PubMedCrossRefGoogle Scholar
  88. Sanz, L., Ayvazyan, N., Calvete, J.J., 2008b. Snake venomics of the Armenian mountain vipers Macrovipera lebetina obtusa and Vipera raddei. J. Proteomics 71, 198–209.PubMedCrossRefGoogle Scholar
  89. Saravia, P., Rojas, E., Arce, V., Guevara, C., López, J.C., Chaves, E., Velásquez, R., Rojas, G., Gutiérrez, J.M., 2002. Geographic and ontogenic variability in the venom of the neotropical rattlesnake Crotalus durissus: pathophysiological and therapeutic implications. Rev. Biol. Trop. 50, 337–346.PubMedGoogle Scholar
  90. Serrano, S.M.T., Shannon, J.D., Wang, D., Camargo, A.C., Fox, J.W., 2005. A multifaceted analysis of viperid snake venoms by two-dimensional gel electrophoresis: an approach to understanding venom proteomics. Proteomics 5, 501–510.PubMedCrossRefGoogle Scholar
  91. Serrano, S.M.T., Fox, J.W., 2008. Exploring snake venom proteomes: multifaceted analyses for complex toxin mixtures. Proteomics 8, 909–920.PubMedCrossRefGoogle Scholar
  92. Stock, R.P., Massougbodji, A., Alagón, A., Chippaux, J-P., 2007. Bringing antivenoms to Sub-Saharan Africa. Nat. Biotech. 2, 173–177.CrossRefGoogle Scholar
  93. Tashima, A.K., Sanz, L., Camargo, A.C.M., Serrano, S.M.T., Calvete, J.J., 2008. Snake venomics of the Brazilian pitvipers Bothrops cotiara and Bothrops fonsecai. Identification of taxonomy markers. J. Proteomics 71, 473–485.PubMedCrossRefGoogle Scholar
  94. Theakston, R.D.G., Warrell, D.A., 2000. Crisis in snake antivenom supply for Africa. Lancet 356, 2104.PubMedCrossRefGoogle Scholar
  95. Thomas, L., Tyburn, B., 1996. The research group of snake bite in Martinique. Bothrops lanceolatus bites in Martinique: clinical aspects and treatment, in: Bon, C., Goyffon, M. (Eds.), Envenomings and Their Treatments. Fondation Marcel Mérieux, Lyon, pp. 255–265.Google Scholar
  96. Valente, R.,H., Guimarães, P.R., Junqueira, M., Neves-Ferreira, A.G.C., Soares, M.R., Chapeaurouge, A., Trugilho, M., León, I.R., Rocha, S., Oliveira-Carvalho, A.L., Serrão, L.W., Dutra, D., Leão, L.I., Junqueira-de-Azevedo, I., Ho, P.L., Zingali, R.B., Perales, J., Domont, G.B., 2009. Bothrops insularis venomics: a proteomic analysis supported by transcriptomic-generated sequence data. J. Proteomics 72, 241–255.PubMedCrossRefGoogle Scholar
  97. Vetter, R.S., Isbister, G.K., 2008. Medical aspects of spider bites. Annu. Rev. Entomol. 53, 409–429.PubMedCrossRefGoogle Scholar
  98. Vidal, N., 2002. Colubroid systematics: evidence for an early appearance of the venom apparatus followed by extensive evolutionary tinkering. J. Toxicol. Toxin Rev. 21, 21–41.CrossRefGoogle Scholar
  99. Wagstaff, S.C., Harrison, R.A., 2006. Venom gland EST analysis of the saw-scaled viper, Echis ocellatus, reveals novel α9β1 integrin-binding motifs in venom metalloproteinases and a new group of putative toxins, renin-like proteases. Gene 377, 21–32.PubMedCrossRefGoogle Scholar
  100. Wagstaff, S.C., Sanz, L., Juárez, P., Harrison, R.A., Calvete, J.J., 2009. Combined snake venomics and venom gland transcriptomic analysis of the ocellated carpet viper, Echis ocellatus. J. Proteomics 71, 609–623.PubMedCrossRefGoogle Scholar
  101. World Health Organization, 2007. Rabies and Envenomings. A Neglected Public Health Issue: Report of a Consultative Meeting. WHO, Geneva. Available:
  102. Wood, D.L., Miljenović, T., Cai, S., Raven, R.J., Kaas, Q., Escoubas, P., Herzig, V., Wilson, D., King, G.F., 2009. ArachnoServer: a database of protein toxins from spiders. BMC Genomics 10, 375.PubMedCrossRefGoogle Scholar
  103. Zhang, B., Liu, Q., Yin, W., Zhang, X., Huang, Y., Luo, Y., Qiu, P., Su, X., Yu, J., Hu, S., Yan, G., 2006. Transcriptome analysis of Deinagkistrodon acutus venomous gland focusing on cellular structure and functional aspects using expressed sequence tags. BMC Genomics 7, 152.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Laboratorio de Proteinómica EstructuralInstituto de Biomedicina de Valencia, CSICValenciaSpain

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