{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T15:14:29Z","timestamp":1783782869348,"version":"3.55.0"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Palearctic vipers are medically significant snakes in the genera <jats:italic>Daboia, Macrovipera, Montivipera<\/jats:italic>, and <jats:italic>Vipera<\/jats:italic> which occur throughout Europe, Central Asia, Near and Middle East. While the ancestral condition is that of a small-bodied, lowland species, extensive diversification has occurred in body size, and niche specialization. Using 27 venom samples and a panel of <jats:italic>in vitro<\/jats:italic> coagulation assays, we evaluated the relative coagulotoxic potency of Palearctic viper venoms and compared their neutralization by three antivenoms (Insoserp Europe, VIPERFAV and ViperaTAb) and two metalloprotease inhibitors (prinomastat and DMPS). We show that variation in morphology parallels variation in the Factor X activating procoagulant toxicity, with the three convergent evolutions of larger body sizes (<jats:italic>Daboia<\/jats:italic> genus, <jats:italic>Macrovipera<\/jats:italic> genus, and <jats:italic>Vipera ammodytes<\/jats:italic> uniquely within the <jats:italic>Vipera<\/jats:italic> genus) were each accompanied by a significant increase in procoagulant potency. In contrast, the two convergent evolutions of high altitude specialization (the <jats:italic>Montivipera<\/jats:italic> genus and <jats:italic>Vipera latastei<\/jats:italic> uniquely within the <jats:italic>Vipera<\/jats:italic> genus) were each accompanied by a shift away from procoagulant action, with the <jats:italic>Montivipera<\/jats:italic> species being particularly potently anticoagulant. Inoserp Europe and VIPERFAV antivenoms were both effective against a broad range of <jats:italic>Vipera<\/jats:italic> species, with Inoserp able to neutralize additional species relative to VIPERFAV, reflective of its more complex antivenom immunization mixture. In contrast, ViperaTAb was extremely potent in neutralizing <jats:italic>V. berus<\/jats:italic> but, reflective of this being a monovalent antivenom, it was not effective against other <jats:italic>Vipera<\/jats:italic> species. The enzyme inhibitor prinomastat efficiently neutralized the metalloprotease-driven Factor X activation of the procoagulant venoms. In contrast, DMPS (2,3-dimercapto-1-propanesulfonic acid), which as been suggested as another potential treatment option in the absence of antivenom, DMPS failed against all venoms tested. Overall, our results highlight the evolutionary variations within Palearctic vipers and help to inform clinical management of viper envenomation.<\/jats:p>","DOI":"10.3389\/fimmu.2021.688802","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T09:30:25Z","timestamp":1623317425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["Venom-Induced Blood Disturbances by Palearctic Viperid Snakes, and Their Relative Neutralization by Antivenoms and Enzyme-Inhibitors"],"prefix":"10.3389","volume":"12","author":[{"given":"Abhinandan","family":"Chowdhury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina N.","family":"Zdenek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Lewin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toma\u017e","family":"Jagar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Ostanek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Harjen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Aldridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Soria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Haw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan G.","family":"Fry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31224-8","article-title":"Vulnerability to Snakebite Envenoming: A Global Mapping of Hotspots","volume":"392","author":"Longbottom","year":"2018","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(19)30225-6\/fulltext","article-title":"Snakebite-Emerging From the Shadows of Neglect","volume":"7","author":"Minghui","year":"2019","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/toxins10040170","article-title":"Snakebite: When the Human Touch Becomes a Bad Touch","volume":"10","author":"Fry","year":"2018","journal-title":"Toxins (Basel)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1146\/annurev.genom.9.081307.164356","article-title":"The Toxicogenomic Multiverse: Convergent Recruitment of Proteins Into Animal Venoms","volume":"10","author":"Fry","year":"2009","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.toxicon.2011.10.008","article-title":"Epidemiology of Snakebites in Europe: A Systematic Review of the Literature","volume":"59","author":"Chippaux","year":"2012","journal-title":"Toxicon"},{"key":"B6","first-page":"1","article-title":"\u201cCritical Care Toxicology,\u201d","volume-title":"Critical Care Toxicology","author":"De Haro","year":"2020"},{"key":"B7","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/0041-0101(92)90854-X","article-title":"Envenoming by Viper Bites in France: Clinical Gradation and Biological Quantification by ELISA","volume":"30","author":"Audebert","year":"1992","journal-title":"Toxicon"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16722","article-title":"Vipera Snakebite in Europe: A Systematic Review of a Neglected Disease","volume":"34","author":"Paolino","year":"2020","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B9","article-title":"Pathophysiology and Treatment of Envenomation by European Vipers","volume-title":"Clinical Toxinology in Asia Pacific and Africa","author":"Persson","year":"2015"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3109\/15563650.2015.1113542","article-title":"Clinical Toxicology Hyperglycemia is a Risk Factor for High-Grade Envenomations After European Viper Bites (Vipera Spp.) in Children","volume":"54","author":"Claudet","year":"2016","journal-title":"Clin Toxicol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/emj.5.2.116","article-title":"Second-Degree Heart Block Associated With Envenomation by","volume":"5","author":"Moore","year":"1988","journal-title":"Vipera berus. 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