{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:18:11Z","timestamp":1790209091722,"version":"4.1.0"},"reference-count":136,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2016,8,26]],"date-time":"2016-08-26T00:00:00Z","timestamp":1472169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"publisher","award":["AuxPE 1214\/2011"],"award-info":[{"award-number":["AuxPE 1214\/2011"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"publisher","award":["BEX 17666\/12-0"],"award-info":[{"award-number":["BEX 17666\/12-0"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CNPq fellow","award":["312311\/2013-3"],"award-info":[{"award-number":["312311\/2013-3"]}]},{"name":"CNPq fellow","award":["311539\/2015-7"],"award-info":[{"award-number":["311539\/2015-7"]}]},{"name":"FAPERJ fellow","award":["E26\/202-960\/2015"],"award-info":[{"award-number":["E26\/202-960\/2015"]}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["Universal 471439\/2011-8"],"award-info":[{"award-number":["Universal 471439\/2011-8"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"publisher","award":["APQ1 E26\/111.781\/2012"],"award-info":[{"award-number":["APQ1 E26\/111.781\/2012"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006507","name":"FIOCRUZ","doi-asserted-by":"publisher","award":["PAPES VI 407611\/2012-6"],"award-info":[{"award-number":["PAPES VI 407611\/2012-6"]}],"id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The research on natural snake venom metalloendopeptidase inhibitors (SVMPIs) began in the 18th century with the pioneering work of Fontana on the resistance that vipers exhibited to their own venom. During the past 40 years, SVMPIs have been isolated mainly from the sera of resistant animals, and characterized to different extents. They are acidic oligomeric glycoproteins that remain biologically active over a wide range of pH and temperature values. Based on primary structure determination, mammalian plasmatic SVMPIs are classified as members of the immunoglobulin (Ig) supergene protein family, while the one isolated from muscle belongs to the ficolin\/opsonin P35 family. On the other hand, SVMPIs from snake plasma have been placed in the cystatin superfamily. These natural antitoxins constitute the first line of defense against snake venoms, inhibiting the catalytic activities of snake venom metalloendopeptidases through the establishment of high-affinity, non-covalent interactions. This review presents a historical account of the field of natural resistance, summarizing its main discoveries and current challenges, which are mostly related to the limitations that preclude three-dimensional structural determinations of these inhibitors using \u201cgold-standard\u201d methods; perspectives on how to circumvent such limitations are presented. Potential applications of these SVMPIs in medicine are also highlighted.<\/jats:p>","DOI":"10.3390\/toxins8090250","type":"journal-article","created":{"date-parts":[[2016,8,26]],"date-time":"2016-08-26T09:58:48Z","timestamp":1472205528000},"page":"250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Natural Inhibitors of Snake Venom Metalloendopeptidases: History and Current Challenges"],"prefix":"10.3390","volume":"8","author":[{"given":"Viviane","family":"Bastos","sequence":"first","affiliation":[{"name":"Laboratory of Toxinology, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"National Institute of Science and Technology on Toxins (INCTTOX), CNPq, Brasilia 71605-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Gomes-Neto","sequence":"additional","affiliation":[{"name":"Laboratory of Toxinology, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"National Institute of Science and Technology on Toxins (INCTTOX), CNPq, Brasilia 71605-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Perales","sequence":"additional","affiliation":[{"name":"Laboratory of Toxinology, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"National Institute of Science and Technology on Toxins (INCTTOX), CNPq, Brasilia 71605-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Neves-Ferreira","sequence":"additional","affiliation":[{"name":"Laboratory of Toxinology, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"National Institute of Science and Technology on Toxins (INCTTOX), CNPq, Brasilia 71605-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6562-7571","authenticated-orcid":false,"given":"Richard","family":"Valente","sequence":"additional","affiliation":[{"name":"Laboratory of Toxinology, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"National Institute of Science and Technology on Toxins (INCTTOX), CNPq, Brasilia 71605-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fraser, T. (1895). Serpent\u2019s Venom: Artificial and Natural Immunity; Antidotal Properties of the Blood-Serum of Immunized Animals and of Venomous Serpents, Neill and Company.","DOI":"10.5962\/bhl.title.101746"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1016\/S0140-6736(12)60846-0","article-title":"The theriac in antiquity","volume":"379","author":"Karaberopoulos","year":"2012","journal-title":"Lancet"},{"key":"ref_3","first-page":"28","article-title":"Theriac: Medicine and antidote","volume":"9","author":"Parojcic","year":"2003","journal-title":"Vesalius"},{"key":"ref_4","first-page":"117","article-title":"Felice Fontana: A forgotten physiologist of the Trentino","volume":"11","author":"Garrison","year":"1935","journal-title":"Bull. N. Y. Acad. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/0041-0101(95)00006-8","article-title":"Abb\u00e9 Felice Fontana (1730\u20131805): Founder of Modern Toxinology","volume":"33","author":"Hawgood","year":"1995","journal-title":"Toxicon"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fontana, F. (1767). Ricerche Fisiche Sopra il Veleno della Vipera con Alcune Offervazioni Sopra la Anguillette dele Grano Sperone, Jacopo Giusti. (In Italian).","DOI":"10.5962\/bhl.title.51612"},{"key":"ref_7","unstructured":"Fontana, F. (1787). Treatise on the Venom of the Viper; on the American Poisons; and on the Cherry Laurel; and Some Other Vegetable Poisons, Jamie Murray."},{"key":"ref_8","first-page":"744","article-title":"Le Venin de Serpents Exerce-t-il sur Eux-m\u00eames l\u2019Action Qu\u2019il Exerce sur D\u2019autres Animaux?","volume":"Volume 2","author":"Phisalix","year":"1861","journal-title":"Animaux Venimeux et Venins: La Fonction Venimeuse chez tous les Animaux; les Appareils Venimeux; les Venins et leurs Propri\u00e9t\u00e9s; les Fonctions et Usages des Venins; L\u2019envenimation et son Traitement"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Calmette, A. (1896). Le Venin des Serpents: Physiologie de l\u2019Envenimation, Traitement des Morsures Venimeuses, Soci\u00e9t\u00e9 d\u2019\u00c9ditions Scientifiques. (In French).","DOI":"10.5962\/bhl.title.11956"},{"key":"ref_10","first-page":"639","article-title":"Recherches sur l\u2019immunit\u00e9 du h\u00e9risson contre le venin de vip\u00e8re","volume":"47","author":"Phisalix","year":"1895","journal-title":"C. R. Soc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1126\/science.78.2010.13.b","article-title":"On the effects of the mocassin venom upon a rattlesnake","volume":"78","author":"Gloyd","year":"1933","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2307\/1438015","article-title":"Effects of crotalid venom on North American snakes","volume":"4","author":"Keegan","year":"1942","journal-title":"Copeia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2307\/1438111","article-title":"Effects of snake venoms on snakes","volume":"4","author":"Swanson","year":"1946","journal-title":"Copeia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3181\/00379727-74-17959","article-title":"Neutralization of pit viper venom by king snake serum","volume":"75","author":"Philpot","year":"1950","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/0041-0101(63)90053-9","article-title":"The Ophiofagus habits of Pseudoboa cloelia","volume":"1","author":"Abalos","year":"1963","journal-title":"Toxicon"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/261259a0","article-title":"Antivenom activity of rattlesnake blood plasma","volume":"261","author":"Straight","year":"1976","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1126\/science.164.3886.1402","article-title":"Venom neutralization by rattlesnake serum albumin","volume":"164","author":"Clark","year":"1969","journal-title":"Science"},{"key":"ref_18","first-page":"463","article-title":"Resistencia de los \u201cDidelphis\u201d (Zarigueya) a los venenos ofidicos (Nota Previa)","volume":"5","author":"Vellard","year":"1945","journal-title":"Rev. Bras. Biol."},{"key":"ref_19","first-page":"1","article-title":"Investigaciones sobre imunidad natural contra los venenos de serpientes","volume":"1","author":"Vellard","year":"1949","journal-title":"I. Publ. Mus. Hist. Nat. Lima Ser. A Zool."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/0041-0101(91)90191-S","article-title":"Natural anti-snake venom proteins","volume":"29","author":"Domont","year":"1991","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.toxicon.2005.02.028","article-title":"Natural inhibitors of snake venom hemorrhagic metalloproteinases","volume":"45","author":"Perales","year":"2005","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0041-0101(01)00274-4","article-title":"Endogenous inhibitors of snake venom phospholipases A(2) in the blood plasma of snakes","volume":"40","year":"2002","journal-title":"Toxicon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.toxicon.2003.11.007","article-title":"Natural phospholipase A2 myotoxin inhibitor proteins from snakes mammals and plants","volume":"42","author":"Lizano","year":"2003","journal-title":"Toxicon"},{"key":"ref_24","first-page":"259","article-title":"Natural Inhibitors\u2014Innate Immunity to Snake Venoms","volume":"Volume 1","author":"Mackessy","year":"2010","journal-title":"Handbook of Venoms and Toxins of Reptiles"},{"key":"ref_25","unstructured":"M\u00e9nez, A. (2002). Perspectives in Molecular Toxinology, John Wiley & Sons."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/S0041-0101(98)00137-8","article-title":"Snake envenomation and protective natural endogenous proteins: A mini review of the recent developments (1991\u20131997)","volume":"36","author":"Thwin","year":"1998","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0041-0101(98)00205-0","article-title":"Natural protease inhibitors to hemorrhagins in snake venoms and their potential use in medicine","volume":"37","author":"Perez","year":"1999","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lima, M.E. (2009). Animal Toxins\u2014State of the Art. Perspectives in Health and Biotechnology, Editora UFMG.","DOI":"10.1590\/S1678-91992009000300021"},{"key":"ref_29","first-page":"1","article-title":"Natural Inhibitors of Snake Venom Metallopeptidases","volume":"Volume 1","author":"Gopalakrishnakone","year":"2016","journal-title":"Toxins and Drug Discovery"},{"key":"ref_30","unstructured":"De Lacerda, J.B. (1884). Le\u00e7ons sur le Venin des Serpents du Br\u00e8sil et sur la M\u00e9thode de Traitement des Morsures Venimeuses par le Permanganate de Potasse, Livraria Lombaerts & C.. (In French)."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/path.1700080402","article-title":"The constitution of snake venom and snake sera","volume":"8","author":"Flexner","year":"1903","journal-title":"J. Pathol. Bacteriol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1348-0421.1960.tb00165.x","article-title":"Studies on habu snake venom. 2c. Studies on H beta-proteinase of habu venom","volume":"4","author":"Maeno","year":"1960","journal-title":"Jpn. J. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"199","DOI":"10.7883\/yoken1952.13.199","article-title":"Fractionation of habu snake venom by chromatography on cm-cellulose with special reference to biological activities","volume":"13","author":"Ohsaka","year":"1960","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"ref_34","first-page":"478","article-title":"Haemorrhagic activities of habu snake venom, and their relations to lethal toxicity, proteolytic activities and other pathological activities","volume":"41","author":"Ohsaka","year":"1960","journal-title":"Br. J. Exp. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1348-0421.1960.tb00167.x","article-title":"Studies on the habu snake venom. 3\u20132. A comparative study of histopathological changes caused by crude venom, purified Habu-proteinase and other proteinases","volume":"4","author":"Okonogi","year":"1960","journal-title":"Jpn. J. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1021\/bi00609a033","article-title":"Hemorrhagic toxins from Western diamondback rattlesnake (Crotalus atrox) venom: Isolation and characterization of five toxins and the role of zinc in hemorrhagic toxin e","volume":"17","author":"Bjarnason","year":"1978","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1111\/j.1742-4658.2008.06466.x","article-title":"Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity","volume":"275","author":"Fox","year":"2008","journal-title":"FEBS J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0300-9084(00)01163-9","article-title":"Snake venom metalloproteinases: Their role in the pathogenesis of local tissue damage","volume":"82","author":"Gutierrez","year":"2000","journal-title":"Biochimie"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s10495-005-2945-1","article-title":"Jararhagin, a snake venom metalloproteinase, induces a specialized form of apoptosis (anoikis) selective to endothelial cells","volume":"10","author":"Tanjoni","year":"2005","journal-title":"Apoptosis"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gutierrez, J.M., Escalante, T., Rucavado, A., and Herrera, C. (2016). Hemorrhage caused by snake venom metalloproteinases: A journey of discovery and understanding. Toxins, 8.","DOI":"10.3390\/toxins8040093"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/S0041-0101(98)00241-4","article-title":"Characterization of local tissue damage evoked by Bothrops jararaca venom in the rat connective tissue microcirculation: An intravital microscopic study","volume":"37","author":"Farsky","year":"1999","journal-title":"Toxicon"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0140-6736(09)61754-2","article-title":"Snake bite","volume":"375","author":"Warrell","year":"2010","journal-title":"Lancet"},{"key":"ref_43","unstructured":"Mackessy, S.P. (2010). Handbook of Venoms and Toxins of Reptiles, CRC Press."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/0005-2795(72)90328-5","article-title":"Purification and characterization of an antihemorrhagic factor in the serum of Trimeresurus flavoviridis, a crotalid","volume":"285","author":"Sadahiro","year":"1972","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0005-2795(77)90243-4","article-title":"Antihemorrhagic factor as a proteinase inhibitor isolated from the serum of Trimeresurus flavoviridis","volume":"495","year":"1977","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/oxfordjournals.jbchem.a123944","article-title":"Primary structure of the antihemorrhagic factor in serum of the Japanese habu: A snake venom metalloproteinase inhibitor with a double-headed cystatin domain","volume":"112","author":"Yamakawa","year":"1992","journal-title":"J. Biochem."},{"key":"ref_47","first-page":"45","article-title":"Efficient Purification of an Antihemorrhagic factor in the serum of Japanese Habu (Trimeresurus flavoviridis)","volume":"33","author":"Deshimaru","year":"2003","journal-title":"Fukuoka Univ. Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.toxicon.2005.09.003","article-title":"Properties and cDNA cloning of an antihemorrhagic factor (HSF) purified from the serum of Trimeresurus flavoviridis","volume":"46","author":"Deshimaru","year":"2005","journal-title":"Toxicon"},{"key":"ref_49","first-page":"177","article-title":"Novel function of antihemorrhagic factor HSF as an SSP-binding protein in habu (Trimeresurus flavoviridis) serum","volume":"41","author":"Shioi","year":"2011","journal-title":"Fukuoka Univ. Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/jb\/mvs127","article-title":"Small serum protein-1 changes the susceptibility of an apoptosis-inducing metalloproteinase HV1 to a metalloproteinase inhibitor in habu snake (Trimeresurus flavoviridis)","volume":"153","author":"Shioi","year":"2012","journal-title":"J. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.toxicon.2006.11.001","article-title":"Active fragments of the antihemorrhagic protein HSF from serum of habu (Trimeresurus flavoviridis)","volume":"49","author":"Aoki","year":"2007","journal-title":"Toxicon"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1006\/bbrc.1994.1706","article-title":"A 28 kDa-protein with disintegrin-like structure (jararhagin-C) purified from Bothrops jararaca venom inhibits collagen- and ADP-induced platelet aggregation","volume":"201","author":"Usami","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1046\/j.1432-1327.2001.02199.x","article-title":"BJ46a, a snake venom metalloproteinase inhibitor. Isolation, characterization, cloning and insights into its mechanism of action","volume":"268","author":"Valente","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s10930-012-9392-y","article-title":"High-level expression, purification, characterization and structural prediction of a snake venom metalloproteinase inhibitor in Pichia pastoris","volume":"31","author":"Shi","year":"2012","journal-title":"Protein J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1097\/CAD.0b013e32835f258d","article-title":"Recombinant snake venom metalloproteinase inhibitor BJ46A inhibits invasion and metastasis of B16F10 and MHCC97H cells through reductions of matrix metalloproteinases 2 and 9 activities","volume":"24","author":"Ji","year":"2013","journal-title":"Anticancer Drugs"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.toxicon.2007.09.007","article-title":"Properties and cDNA cloning of antihemorrhagic factors in sera of Chinese and Japanese mamushi (Gloydius blomhoffi)","volume":"51","author":"Aoki","year":"2008","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1080\/09168451.2014.890030","article-title":"Structural analysis and characterization of new small serum proteins from the serum of a venomous snake (Gloydius blomhoffii)","volume":"78","author":"Shioi","year":"2014","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"31496","DOI":"10.1074\/jbc.272.50.31496","article-title":"Cloning and targeted deletion of the mouse fetuin gene","volume":"272","author":"Schinke","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.toxicon.2009.05.018","article-title":"Snake fetuin: Isolation and structural analysis of new fetuin family proteins from the sera of venomous snakes","volume":"54","author":"Aoki","year":"2009","journal-title":"Toxicon"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"777","DOI":"10.2307\/1446405","article-title":"Observations on a venom neutralizing fraction isolated from the serum of the Northern Copperhead","volume":"5","author":"Weinstein","year":"1991","journal-title":"Agkistrodon Contortrix Mokasen Copeia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/0304-4165(95)00081-L","article-title":"Isolation, characterization and mode of neutralization of a potent antihemorrhagic factor from the serum of the snake Bothrops asper","volume":"1245","author":"Borkow","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/0041-0101(91)90217-F","article-title":"Antihemorrhagic factors in the blood serum of the western diamondback rattlesnake Crotalus atrox","volume":"29","author":"Weissenberg","year":"1991","journal-title":"Toxicon"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/0041-0101(92)90853-W","article-title":"Inhibition of the proteolytic activity of hemorrhagin-e from Crotalus atrox serum by antihemorrhagins from homologous serum","volume":"30","author":"Weissenberg","year":"1992","journal-title":"Toxicon"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/0041-0101(90)90028-6","article-title":"Neutralization of hemorrhagic snake venoms by sera of Trimeresurus flavoviridis (habu), Herpestes edwardsii (mongoose) and Dinodon semicarinatus (akamata)","volume":"28","author":"Tomihara","year":"1990","journal-title":"Toxicon"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/0304-4165(94)90080-9","article-title":"A potent antihemorrhagin in the serum of the non-poisonous water snake Natrix tessellata: Isolation, characterization and mechanism of neutralization","volume":"1201","author":"Borkow","year":"1994","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1006\/bbrc.1999.1421","article-title":"Isolation and characterization of a novel proteinase inhibitor from the snake serum of Taiwan Habu (Trimeresurus mucrosquamatus)","volume":"263","author":"Huang","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/0041-0101(78)90194-0","article-title":"Purification and characterization of an antihemorrhagic factor from the serum of the snake Vipera palaestinae","volume":"16","author":"Ovadia","year":"1978","journal-title":"Toxicon"},{"key":"ref_68","unstructured":"Azara, F.D. (1802). Apuntamientos para la Historia Natural de los Quadr\u00fapedos del Parag\u00fcay y R\u00edo de la Plata, Imprenta de la Viuda de Ibarra. (In Spanish)."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1111\/j.1469-185X.2012.00222.x","article-title":"Snake-venom resistance as a mammalian trophic adaptation: Lessons from didelphid marsupials","volume":"87","author":"Voss","year":"2012","journal-title":"Biol. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0041-0101(76)90032-5","article-title":"High tolerance to snake venom by the Virginia opossum, Didelphis virginiana","volume":"14","author":"Kilmon","year":"1976","journal-title":"Toxicon"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/0041-0101(81)90100-8","article-title":"The purification and characterization of an antihemorrhagic factor in opossum (Didelphis virginiana) serum","volume":"19","author":"Menchaca","year":"1981","journal-title":"Toxicon"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1021\/bi00117a015","article-title":"Isolation from opossum serum of a metalloproteinase inhibitor homologous to human alpha 1B-glycoprotein","volume":"31","author":"Catanese","year":"1992","journal-title":"Biochemistry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/0041-0101(87)90117-6","article-title":"Purification of three antihemorrhagic factors from the serum of a mongoose (Herpestes edwardsii)","volume":"25","author":"Tomihara","year":"1987","journal-title":"Toxicon"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/0041-0101(94)90417-0","article-title":"Characterization of the antihemorrhagic factors of mongoose (Herpestes edwardsii)","volume":"32","author":"Qi","year":"1994","journal-title":"Toxicon"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0041-0101(94)00146-Y","article-title":"Isolation of peptides homologous to domains of human alpha 1B-glycoprotein from a mongoose antihemorrhagic factor","volume":"33","author":"Qi","year":"1995","journal-title":"Toxicon"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/0041-0101(94)90353-0","article-title":"Isolation and partial characterization of an anti-bothropic complex from the serum of the south american Didelphidae","volume":"32","author":"Perales","year":"1994","journal-title":"Toxicon"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.toxicon.2003.08.006","article-title":"PO41, a snake venom metalloproteinase inhibitor isolated from Philander opossum serum","volume":"42","author":"Jurgilas","year":"2003","journal-title":"Toxicon"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/0041-0101(96)00034-7","article-title":"Isolation of protein factors from opossum (Didelphis albiventris) serum which protect against Bothrops jararaca venom","volume":"34","author":"Farah","year":"1996","journal-title":"Toxicon"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/0041-0101(79)90130-2","article-title":"Mechanisms of resistance of the opossum to some snake venoms","volume":"17","author":"Yates","year":"1979","journal-title":"Toxicon"},{"key":"ref_80","first-page":"104","article-title":"Obtenci\u00f3n de una fracci\u00f3n del suero de Didelphis activa contra la acci\u00f3n t\u00f3xica del veneno de B. jararaca","volume":"31","author":"Yates","year":"1980","journal-title":"Acta Cient. Venez."},{"key":"ref_81","first-page":"173","article-title":"Inhibici\u00f3n por una prote\u00edna aislada del suero de D. marsupialis a la acci\u00f3n hemorrh\u00e1gica por una fracci\u00f3n del veneno de Bothrops jararaca","volume":"32","author":"Leonardi","year":"1981","journal-title":"Acta Cient. Venez."},{"key":"ref_82","first-page":"155","article-title":"Isolation and partial characterization of a protein fraction from the opossum (Didelphis marsupialis) serum, with protecting property against Bothrops jararaca venom","volume":"58","author":"Perales","year":"1986","journal-title":"An. Acad. Bras. Cienc."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1590\/S0074-02761989000800070","article-title":"Factors underlying the natural resistance of animals against snake venoms","volume":"84","author":"Perales","year":"1989","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/BF02028117","article-title":"Neutralization of the oedematogenic activity of Bothrops jararaca venom on the mouse paw by a antibothropic fraction isolated from opossum (Didelphis marsupialis) serum","volume":"37","author":"Perales","year":"1992","journal-title":"Agents Actions"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0041-0101(99)00190-7","article-title":"Inhibition of the hyperalgesic activity of Bothrops jararaca venom by an antibothropic fraction isolated from opossum (Didelphis marsupialis) serum","volume":"38","author":"Rocha","year":"2000","journal-title":"Toxicon"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0041-0101(96)00195-X","article-title":"Inhibitory properties of the antibothropic complex from the south american opossum (Didelphis marsupialis) serum","volume":"35","author":"Perales","year":"1997","journal-title":"Toxicon"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0041-0101(98)00175-5","article-title":"Detection of an antibothropic fraction in opossum (Didelphis marsupialis) milk that neutralizes Bothrops jararaca venom","volume":"37","author":"Jurgilas","year":"1999","journal-title":"Toxicon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0304-4165(00)00022-2","article-title":"Isolation and characterization of DM40 and DM43, two snake venom metalloproteinase inhibitors from Didelphis marsupialis serum","volume":"1474","author":"Cardinale","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"13129","DOI":"10.1074\/jbc.M200589200","article-title":"Structural and functional analyses of DM43, a snake venom metalloproteinase inhibitor from Didelphis marsupialis serum","volume":"277","author":"Perales","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.1002\/pmic.201200062","article-title":"Using mass spectrometry to explore the neglected glycan moieties of the antiophidic proteins DM43 and DM64","volume":"12","author":"Rocha","year":"2012","journal-title":"Proteomics"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/jms.2990","article-title":"The interaction of the antitoxin DM43 with a snake venom metalloproteinase analyzed by mass spectrometry and surface plasmon resonance","volume":"47","author":"Brand","year":"2012","journal-title":"J. Mass Spectrom."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ab.2003.12.025","article-title":"Characterizing high-affinity antigen\/antibody complexes by kinetic- and equilibrium-based methods","volume":"328","author":"Drake","year":"2004","journal-title":"Anal. Biochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1021\/pr800977s","article-title":"Crotalid snake venom subproteomes unraveled by the antiophidic protein DM43","volume":"8","author":"Rocha","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxicon.2014.01.001","article-title":"Interaction of Bothrops jararaca venom metalloproteinases with protein inhibitors","volume":"80","author":"Asega","year":"2014","journal-title":"Toxicon"},{"key":"ref_95","unstructured":"Jurgilas, P.B., de Meis, J., Valente, R.H., Neves-Ferreira, A.G.C., da Cruz, D.A.M., de Oliveira, D.A.F., Savino, W., Domont, G.B., and Perales, J. (2008). Use of DM43 and Its Fragments as Matrix Metalloproteinases Inhibitor. (20080249005 A1), U.S. Patent."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/S0041-0101(96)00104-3","article-title":"Erinacin, an antihemorrhagic factor from the european hedgehog, Erinaceus europaeus","volume":"34","author":"Mebs","year":"1996","journal-title":"Toxicon"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"14220","DOI":"10.1074\/jbc.272.22.14220","article-title":"Two oligomeric forms of plasma ficolin have differential lectin activity","volume":"272","author":"Ohashi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"20721","DOI":"10.1074\/jbc.273.33.20721","article-title":"Cloning and characterization of the Hakata antigen, a member of the ficolin\/opsonin p35 lectin family","volume":"273","author":"Sugimoto","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/S0041-0101(00)00090-8","article-title":"The antihemorrhagic factor, erinacin, from the European hedgehog (Erinaceus europaeus), a metalloprotease inhibitor of large molecular size possessing ficolin\/opsonin P35 lectin domains","volume":"38","author":"Yamakawa","year":"2000","journal-title":"Toxicon"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1074\/jbc.271.5.2448","article-title":"A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin","volume":"271","author":"Matsushita","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1042\/bj2900205","article-title":"Evolutionary families of peptidases","volume":"290","author":"Rawlings","year":"1993","journal-title":"Biochem. J."},{"key":"ref_102","unstructured":"Mackessy, S.P. (2010). Handbook of Venoms and Toxins of Reptiles, CRC Press."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nri3499","article-title":"Metalloproteinases and their natural inhibitors in inflammation and immunity","volume":"13","author":"Khokha","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0041-0101(02)00389-6","article-title":"Assessment of efficacy of bothropic antivenom therapy on microcirculatory effects induced by Bothrops jararaca snake venom","volume":"41","author":"Battellino","year":"2003","journal-title":"Toxicon"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2165\/00003088-200342080-00002","article-title":"Pharmacokinetic-pharmacodynamic relationships of immunoglobulin therapy for envenomation","volume":"42","author":"Gutierrez","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.2174\/138161207782023784","article-title":"Trends in snakebite envenomation therapy: Scientific, technological and public health considerations","volume":"13","author":"Gutierrez","year":"2007","journal-title":"Curr. Pharm. Des."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1021\/bi00815a005","article-title":"Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom","volume":"9","author":"Ferreira","year":"1970","journal-title":"Biochemistry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1021\/bi00798a004","article-title":"Angiotensin-converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis","volume":"10","author":"Ondetti","year":"1971","journal-title":"Biochemistry"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1056\/NEJM197410172911603","article-title":"An angiotensin converting-enzyme inhibitor to identify and treat vasoconstrictor and volume factors in hypertensive patients","volume":"291","author":"Gavras","year":"1974","journal-title":"N. Engl. J. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/13423","article-title":"Design of angiotensin converting enzyme inhibitors","volume":"5","author":"Cushman","year":"1999","journal-title":"Nat. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5484","DOI":"10.1021\/bi00644a014","article-title":"Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids","volume":"16","author":"Cushman","year":"1977","journal-title":"Biochemistry"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1126\/science.191908","article-title":"Design of specific inhibitors of angiotensin-converting enzyme: New class of orally active antihypertensive agents","volume":"196","author":"Ondetti","year":"1977","journal-title":"Science"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrd1227","article-title":"ACE revisited: A new target for structure-based drug design","volume":"2","author":"Acharya","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/cbdd.12055","article-title":"The future of peptide-based drugs","volume":"81","author":"Craik","year":"2013","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/1573406053402569","article-title":"Protease inhibitors in the clinic","volume":"1","author":"Abbenante","year":"2005","journal-title":"Med. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1440-1827.2010.02547.x","article-title":"Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases","volume":"60","author":"Shiomi","year":"2010","journal-title":"Pathol. Int."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nrd3053","article-title":"Emerging principles in protease-based drug discovery","volume":"9","author":"Drag","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"15935","DOI":"10.1074\/jbc.M112.341156","article-title":"Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: Binding studies and crystal structure","volume":"287","author":"Batra","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1742-4658.2007.06178.x","article-title":"Protein crystallography for non-crystallographers, or how to get the best (but not more) from published macromolecular structures","volume":"275","author":"Wlodawer","year":"2008","journal-title":"FEBS J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10858-009-9362-7","article-title":"Recent advances in segmental isotope labeling of proteins: NMR applications to large proteins and glycoproteins","volume":"46","author":"Skrisovska","year":"2010","journal-title":"J. Biomol. NMR"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"12366","DOI":"10.1073\/pnas.94.23.12366","article-title":"Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution","volume":"94","author":"Pervushin","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/prot.340090107","article-title":"Database of homology-derived protein structures and the structural meaning of sequence alignment","volume":"9","author":"Sander","year":"1991","journal-title":"Proteins"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"6073","DOI":"10.1073\/pnas.95.11.6073","article-title":"Assessing sequence comparison methods with reliable structurally identified distant evolutionary relationships","volume":"95","author":"Brenner","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/protein\/12.2.85","article-title":"Twilight zone of protein sequence alignments","volume":"12","author":"Rost","year":"1999","journal-title":"Protein Eng."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1126\/science.1853201","article-title":"A method to identify protein sequences that fold into a known three-dimensional structure","volume":"253","author":"Bowie","year":"1991","journal-title":"Science"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/358086a0","article-title":"A new approach to protein fold recognition","volume":"358","author":"Jones","year":"1992","journal-title":"Nature"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.sbi.2008.02.004","article-title":"Progress and challenges in protein structure prediction","volume":"18","author":"Zhang","year":"2008","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Boratyn, G.M., Schaffer, A.A., Agarwala, R., Altschul, S.F., Lipman, D.J., and Madden, T.L. (2012). Domain enhanced lookup time accelerated BLAST. Biol. Direct., 7.","DOI":"10.1186\/1745-6150-7-12"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/jmbi.1999.3091","article-title":"Protein secondary structure prediction based on position-specific scoring matrices","volume":"292","author":"Jones","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1006\/jmbi.1999.2583","article-title":"GenTHREADER: An efficient and reliable protein fold recognition method for genomic sequences","volume":"287","author":"Jones","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER Suite: Protein structure and function prediction","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Kahraman, A., Herzog, F., Leitner, A., Rosenberger, G., Aebersold, R., and Malmstrom, L. (2013). Cross-link guided molecular modeling with ROSETTA. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073411"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5619","DOI":"10.1021\/bi500420y","article-title":"Structural analysis of diheme cytochrome c by hydrogen-deuterium exchange mass spectrometry and homology modeling","volume":"53","author":"Zhang","year":"2014","journal-title":"Biochemistry"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Schneidman-Duhovny, D., Kim, S.J., and Sali, A. (2012). Integrative structural modeling with small angle X-ray scattering profiles. BMC Struct. Biol., 12.","DOI":"10.1186\/1472-6807-12-17"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1006\/jmbi.2001.5324","article-title":"Protein structure prediction constrained by solution X-ray scattering data and structural homology identification","volume":"316","author":"Zheng","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.bpj.2013.07.020","article-title":"Accurate SAXS profile computation and its assessment by contrast variation experiments","volume":"105","author":"Hammel","year":"2013","journal-title":"Biophys. J."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/8\/9\/250\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:29:21Z","timestamp":1760210961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/8\/9\/250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,26]]},"references-count":136,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2016,9]]}},"alternative-id":["toxins8090250"],"URL":"https:\/\/doi.org\/10.3390\/toxins8090250","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,26]]}}}