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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Sousa, Leijiane F. [1, 2] ; Bernardoni, Juliana L. [1] ; Zdenek, Christina N. [2] ; Dobson, James [2] ; Coimbra, Francisco [2] ; Gillett, Amber [3] ; Lopes-Ferreira, Monica [4] ; Moura-da-Silva, A. M. [1] ; Fry, Bryan G. [2]
Total Authors: 9
Affiliation:
[1] Inst Butantan, Lab Imunopatol, Sao Paulo, SP - Brazil
[2] Univ Queensland, Sch Biol Sci, Toxin Evolut Lab, Santa Lucia, Qld 4072 - Australia
[3] Fauna Vet Wildlife Vet Consultancy, Beerwah, Qld - Australia
[4] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling, Immunoregulat Unit Special Lab Appl Toxinol, Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Toxicology Letters; v. 333, p. 211-221, OCT 15 2020.
Web of Science Citations: 0
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. (AU)

FAPESP's process: 12/23018-0 - Adaptative advantages of the presence of different metalloproteinases in the composition of Bothrops venoms and implications of this variability in snakebites
Grantee:Juliana Lech Bernardoni
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 17/15170-0 - Characterization of mechanisms involved in the hemostatic disturbances induced by Bothrops atrox venoms from three locations of Brazilian Amazon
Grantee:Leijiane Figueira de Sousa
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 14/13124-2 - Variability in Bothrops atrox snake venom from Western Pará: implications for snake ecology and pathophysiology of envenoming
Grantee:Leijiane Figueira de Sousa
Support Opportunities: Scholarships in Brazil - Doctorate