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Differential coagulotoxicity of metalloprotease isoforms from Bothrops neuwiedi snake venom and consequent variations in antivenom efficacy.

Authors
  • Sousa, Leijiane F1
  • Bernardoni, Juliana L2
  • Zdenek, Christina N3
  • Dobson, James3
  • Coimbra, Francisco3
  • Gillett, Amber4
  • Lopes-Ferreira, Mônica5
  • Moura-da-Silva, A M6
  • Fry, Bryan G7
  • 1 Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil; Toxin Evolution Lab, School of Biological Sciences, University of Queensland, Santa Lucia, QLD 4072, Australia. , (Australia)
  • 2 Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil. , (Brazil)
  • 3 Toxin Evolution Lab, School of Biological Sciences, University of Queensland, Santa Lucia, QLD 4072, Australia. , (Australia)
  • 4 Fauna Vet Wildlife Veterinary Consultancy, Beerwah, QLD, Australia. , (Australia)
  • 5 Immunoregulation Unit of the Special Laboratory of Applied Toxinology (Center of Toxins Immune-Response and Cell Signaling), Butantan Institute, São Paulo, SP, Brazil. , (Brazil)
  • 6 Laboratório de Imunopatologia, Instituto Butantan, São Paulo, SP, Brazil. Electronic address: [email protected] , (Brazil)
  • 7 Toxin Evolution Lab, School of Biological Sciences, University of Queensland, Santa Lucia, QLD 4072, Australia. Electronic address: [email protected] , (Australia)
Type
Published Article
Journal
Toxicology letters
Publication Date
Aug 22, 2020
Volume
333
Pages
211–221
Identifiers
DOI: 10.1016/j.toxlet.2020.08.009
PMID: 32841740
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Bothrops (lance-head pit vipers) venoms are rich in weaponised metalloprotease enzymes (SVMP). These toxic enzymes are structurally diverse and functionally versatile. Potent coagulotoxicity is particularly important for prey capture (via stroke-induction) and relevant to human clinical cases (due to consumption of clotting factors including the critical depletion of fibrinogen). In this study, three distinct isoforms of P-III class SVMPs (IC, IIB and IIC), isolated from Bothrops neuwiedi venom, were evaluated for their differential capacities to affect hemostasis of prey and human plasma. Furthermore, we tested the relative antivenom neutralisation of effects upon human plasma. The toxic enzymes displayed differential procoagulant potency between plasma types, and clinically relevant antivenom efficacy variations were observed. Of particular importance was the confirmation the antivenom performed better against prothrombin activating toxins than Factor X activating toxins, which is likely due to the greater prevalence of the former in the immunising venoms used for antivenom production. This is clinically relevant as the enzymes displayed differential potency in this regard, with one (IC) in particular being extremely potent in activating Factor X and thus was correspondingly poorly neutralised. This study broadens the current understanding about the adaptive role of the SVMPs, as well as highlights how the functional diversity of SVMP isoforms can influence clinical outcomes. Key Contribution: Our findings shed light upon the hemorrhagic and coagulotoxic effects of three SVMPs of the P-III class, as well as the coagulotoxic effects of SVMPs on human, avian and amphibian plasmas. Antivenom neutralised prothrombin-activating isoforms better than Factor X activating isoforms. Copyright © 2020 Elsevier B.V. All rights reserved.

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