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Venomous Landmines: Clinical Implications of Extreme Coagulotoxic Diversification and Differential Neutralization by Antivenom of Venoms within the Viperid Snake Genus Bitis
Open AccessArticle

Antivenom Neutralization of Coagulopathic Snake Venom Toxins Assessed by Bioactivity Profiling Using Nanofractionation Analytics

Division of BioAnalytical Chemistry, Amsterdam Institute of Molecular and Life Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
Centre for Analytical Sciences Amsterdam (CASA), 1098 XH Amsterdam, The Netherlands
Centre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK
Naturalis Biodiversity Center, 2333 CR Leiden, The Netherlands
Author to whom correspondence should be addressed.
Toxins 2020, 12(1), 53; (registering DOI)
Received: 19 November 2019 / Revised: 9 January 2020 / Accepted: 13 January 2020 / Published: 16 January 2020
Venomous snakebite is one of the world’s most lethal neglected tropical diseases. Animal-derived antivenoms are the only standardized specific therapies currently available for treating snakebite envenoming, but due to venom variation, often this treatment is not effective in counteracting all clinical symptoms caused by the multitude of injected toxins. In this study, the coagulopathic toxicities of venoms from the medically relevant snake species Bothrops asper, Calloselasma rhodostoma, Deinagkistrodon acutus, Daboia russelii, Echis carinatus and Echis ocellatus were assessed. The venoms were separated by liquid chromatography (LC) followed by nanofractionation and parallel mass spectrometry (MS). A recently developed high-throughput coagulation assay was employed to assess both the pro- and anticoagulant activity of separated venom toxins. The neutralization capacity of antivenoms on separated venom components was assessed and the coagulopathic venom peptides and enzymes that were either neutralized or remained active in the presence of antivenom were identified by correlating bioassay results with the MS data and with off-line generated proteomics data. The results showed that most snake venoms analyzed contained both procoagulants and anticoagulants. Most anticoagulants were identified as phospholipases A2s (PLA2s) and most procoagulants correlated with snake venom metalloproteinases (SVMPs) and serine proteases (SVSPs). This information can be used to better understand antivenom neutralization and can aid in the development of next-generation antivenom treatments. View Full-Text
Keywords: antivenom; nanofractionation; coagulation; anticoagulation; snakebite antivenom; nanofractionation; coagulation; anticoagulation; snakebite
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Xie, C.; Slagboom, J.; Albulescu, L.-O.; Bruyneel, B.; Still, K.B.M.; Vonk, F.J.; Somsen, G.W.; Casewell, N.R.; Kool, J. Antivenom Neutralization of Coagulopathic Snake Venom Toxins Assessed by Bioactivity Profiling Using Nanofractionation Analytics. Toxins 2020, 12, 53.

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