{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:22:52Z","timestamp":1777501372597,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["FORDECYT no.303045"],"award-info":[{"award-number":["FORDECYT no.303045"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>A fundamental issue of the characterization of single-chain variable fragments (scFvs), capable of neutralizing scorpion toxins, is their cross-neutralizing ability. This aspect is very important in Mexico because all scorpions dangerous to humans belong to the Centruroides genus, where toxin sequences show high identity. Among toxin-neutralizing antibodies that were generated in a previous study, scFv 10FG2 showed a broad cross-reactivity against several Centruroides toxins, while the one of scFv LR is more limited. Both neutralizing scFvs recognize independent epitopes of the toxins. In the present work, the neutralization capacity of these two scFvs against two medically important toxins of the venom of Centruroides sculpturatus Ewing was evaluated. The results showed that these toxins are recognized by both scFvs with affinities between 1.8 \u00d7 10\u22129 and 6.1 \u00d7 10\u221211 M. For this reason, their ability to neutralize the venom was evaluated in mice, where scFv 10FG2 showed a better protective capacity. A combination of both scFvs at a molar ratio of 1:5:5 (toxins: scFv 10FG2: scFv LR) neutralized the venom without the appearance of any signs of intoxication. These results indicate a complementary activity of these two scFvs during venom neutralization.<\/jats:p>","DOI":"10.3390\/toxins13100708","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T01:59:47Z","timestamp":1633917587000},"page":"708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Full Neutralization of Centruroides sculpturatus Scorpion Venom by Combining Two Human Antibody Fragments"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2531-9232","authenticated-orcid":false,"given":"Lidia","family":"Ria\u00f1o-Umbarila","sequence":"first","affiliation":[{"name":"CONACYT, Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Alberto","family":"Romero-Moreno","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis M.","family":"Ledezma-Candanoza","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timoteo","family":"Olamendi-Portugal","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourival D.","family":"Possani","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baltazar","family":"Becerril","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnolog\u00eda, Departamento de Medicina Molecular y Bioprocesos, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.actatropica.2018.08.002","article-title":"North American scorpion species of public health importance with a reappraisal of historical epidemiology","volume":"187","author":"Possani","year":"2018","journal-title":"Acta Trop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.2105\/AJPH.2017.304094","article-title":"Geographic Distribution of Scorpion Exposures in the United States, 2010\u20132015","volume":"107","author":"Kang","year":"2017","journal-title":"Am. J. Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1080\/15563650.2020.1834219","article-title":"2019 Annual Report of the American Association of Poison Control Centers\u2019 National Poison Data System (NPDS): 37th Annual Report","volume":"58","author":"Gummin","year":"2020","journal-title":"Clin. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.toxicon.2017.08.022","article-title":"Updating knowledge on new medically important scorpion species in Mexico","volume":"138","author":"Guereca","year":"2017","journal-title":"Toxicon"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.abb.2017.12.012","article-title":"Intraspecific variation of Centruroides sculpturatus scorpion venom from two regions of Arizona","volume":"638","author":"Rowe","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.toxicon.2020.05.021","article-title":"Biochemical, electrophysiological and immunological characterization of the venom from Centruroides baergi, a new scorpion species of medical importance in Mexico","volume":"184","author":"Possani","year":"2020","journal-title":"Toxicon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.peptides.2016.11.008","article-title":"Functional and immuno-reactive characterization of a previously undescribed peptide from the venom of the scorpion Centruroides limpidus","volume":"87","author":"Becerril","year":"2017","journal-title":"Peptides"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.toxicon.2011.12.003","article-title":"Negative-shift activation, current reduction and resurgent currents induced by beta-toxins from Centruroides scorpions in sodium channels","volume":"59","author":"Schiavon","year":"2012","journal-title":"Toxicon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.toxicon.2013.07.017","article-title":"Safety of intravenous equine F(ab\u2019)2: Insights following clinical trials involving 1534 recipients of scorpion antivenom","volume":"76","author":"Boyer","year":"2013","journal-title":"Toxicon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1111\/j.1742-4658.2005.04687.x","article-title":"A strategy for the generation of specific human antibodies by directed evolution and phage display. An example of a single-chain antibody fragment that neutralizes a major component of scorpion venom","volume":"272","author":"Possani","year":"2005","journal-title":"FEBS J."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Riano-Umbarila, L., Gomez-Ramirez, I.V., Ledezma-Candanoza, L.M., Olamendi-Portugal, T., Rodriguez-Rodriguez, E.R., Fernandez-Taboada, G., Possani, L.D., and Becerril, B. (2019). Generation of a Broadly Cross-Neutralizing Antibody Fragment against Several Mexican Scorpion Venoms. Toxins, 11.","DOI":"10.3390\/toxins11010032"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6143","DOI":"10.1074\/jbc.M110.189175","article-title":"Exploiting cross-reactivity to neutralize two different scorpion venoms with one single chain antibody fragment","volume":"286","author":"Corzo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.toxicon.2020.06.011","article-title":"The three-dimensional structure of the toxic peptide Cl13 from the scorpion Centruroides limpidus","volume":"184","author":"Becerril","year":"2020","journal-title":"Toxicon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1006\/jmbi.1999.2611","article-title":"Solution structure of toxin 2 from centruroides noxius Hoffmann, a beta-scorpion neurotoxin acting on sodium channels","volume":"287","author":"Pintar","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.bbapap.2012.01.003","article-title":"Solution structure of native and recombinant expressed toxin CssII from the venom of the scorpion Centruroides suffusus suffusus, and their effects on Nav1.5 sodium channels","volume":"1824","author":"Saucedo","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.molimm.2020.04.015","article-title":"Comparative assessment of the VH-VL and VL-VH orientations of single-chain variable fragments of scorpion toxin-neutralizing antibodies","volume":"122","author":"Costas","year":"2020","journal-title":"Mol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1074\/jbc.M115.685297","article-title":"Optimal Neutralization of Centruroides noxius Venom Is Understood through a Structural Complex between Two Antibody Fragments and the Cn2 Toxin","volume":"291","author":"Possani","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.toxicon.2016.05.011","article-title":"Broadening the neutralizing capacity of a family of antibody fragments against different toxins from Mexican scorpions","volume":"119","author":"Possani","year":"2016","journal-title":"Toxicon"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.3389\/fimmu.2019.01598","article-title":"History of Envenoming Therapy and Current Perspectives","volume":"10","author":"Pucca","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.toxicon.2019.06.005","article-title":"Engineering and design considerations for next-generation snakebite antivenoms","volume":"167","author":"Knudsen","year":"2019","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Knudsen, C., Casewell, N.R., Lomonte, B., Gutierrez, J.M., Vaiyapuri, S., and Laustsen, A.H. (2020). Novel Snakebite Therapeutics Must Be Tested in Appropriate Rescue Models to Robustly Assess Their Preclinical Efficacy. Toxins, 12.","DOI":"10.3390\/toxins12090528"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.toxicon.2018.03.004","article-title":"Pros and cons of different therapeutic antibody formats for recombinant antivenom development","volume":"146","author":"Laustsen","year":"2018","journal-title":"Toxicon"},{"key":"ref_23","unstructured":"(2021). Schr\u00f6dinger Release 2021-1, Maestro, Schr\u00f6dinger, LLC."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Chow, D.E., Xu, H., Dror, R.O., Eastwood, M.P., Gregersen, B.A., Klepeis, J.L., Kolossvary, I., Moraes, M.A., and Sacerdoti, F.D. (2006, January 11\u201317). Scalable algorithms for molecular dynamics simulations on commodity clusters. Proceedings of the SC \u201806: Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing, Tampa, FL, USA.","DOI":"10.1145\/1188455.1188544"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"W473","DOI":"10.1093\/nar\/gkm423","article-title":"PIC: Protein Interactions Calculator","volume":"35","author":"Tina","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jmb.2007.05.022","article-title":"Inference of macromolecular assemblies from crystalline state","volume":"372","author":"Krissinel","year":"2007","journal-title":"J. Mol. Biol."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/10\/708\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:10:01Z","timestamp":1760166601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/10\/708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,6]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["toxins13100708"],"URL":"https:\/\/doi.org\/10.3390\/toxins13100708","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,6]]}}}