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scholarship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The evolution of snake venoms resulted in multigene toxin families that code for structurally similar isoforms eventually harboring distinct functions. PLA2s are dominant toxins in viper venoms, and little is known about the impact of their diversity on human envenomings and neutralization by antivenoms. Here, we show the isolation of three distinct PLA2s from B. atrox venom. FA1 is a Lys-49 homologue, and FA3 and FA4 are catalytic Asp-49 PLA2s. FA1 and FA3 are basic myotoxic proteins, while FA4 is an acid non-myotoxic PLA2. FA3 was the most potent toxin, inducing higher levels of edema, inflammatory nociception, indirect hemolysis, and anticoagulant activity on human, rat, and chicken plasmas. FA4 presented lower anticoagulant activity, and FA1 had only a slight effect on human and rat plasmas. PLA2s presented differential reactivities with antivenoms, with an emphasis on FA3, which was not recognized or neutralized by the antivenoms used in this study. Our findings reveal the functional and antigenic diversity among PLA2s from B. atrox venom, highlighting the importance of assessing venom variability for understanding human envenomations and treatment with antivenoms, particularly evident here as the antivenom fails to recognize FA3, the most active multifunctional toxin described.<\/jats:p>","DOI":"10.3390\/toxins14080543","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T09:47:06Z","timestamp":1660124826000},"page":"543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Diversity of Phospholipases A2 from Bothrops atrox Snake Venom: Adaptive Advantages for Snakes Compromising Treatments for Snakebite Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-0897","authenticated-orcid":false,"given":"Leijiane F.","family":"Sousa","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Butantan, Av. Vital Brazil, 1500, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda P.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Butantan, Av. Vital Brazil, 1500, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna L.","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Butantan, Av. Vital Brazil, 1500, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago H. M.","family":"Del-Rei","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Butantan, Av. Vital Brazil, 1500, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa A.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Dor e Sinaliza\u00e7\u00e3o, Instituto Butantan, Av. Vital Brazil, 1500, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele P.","family":"Or\u00e9fice","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Butantan, Av. Vital Brazil, 1500, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa M. T.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Herpetologia, Instituto Butantan, Av. Vital Brazil, 1500, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-3668","authenticated-orcid":false,"given":"Benedito C.","family":"Prezoto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Instituto Butantan, Av. Vital Brazil, 1500, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1787-6634","authenticated-orcid":false,"given":"Ana M.","family":"Moura-da-Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Butantan, Av. 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