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

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Xie, C, Slagboom, J, Albulescu, Laura-Oana, Bruyneel, B, Still, KBM, Vonk, FJ, Somsen, GW, Casewell, Nicholas ORCID: https://orcid.org/0000-0002-8035-4719 and Kool, J (2020) 'Antivenom Neutralization of Coagulopathic Snake Venom Toxins Assessed by Bioactivity Profiling Using Nanofractionation Analytics'. Toxins, Vol 12, Issue 1, p. 53.

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Abstract

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.

Item Type: Article
Additional Information: This article belongs to the Special Issue Medically Relevant Snake Toxins, Current Antivenoms and the Development of Next-Generation Antivenoms
Subjects: QV Pharmacology > Hematologic Agents > QV 195 Hemostatics. Coagulants
QV Pharmacology > QV 38 Drug action.
QV Pharmacology > QV 4 General works
QY Clinical Pathology > Blood. Blood Chemistry > QY 410 Coagulation
WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.3390/toxins12010053
Depositing User: Mary Creegan
Date Deposited: 17 Jan 2020 16:07
Last Modified: 23 Jan 2020 11:30
URI: https://archive.lstmed.ac.uk/id/eprint/13543

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