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Extreme Procoagulant Potency in Human Plasma of Venoms from the African Viperid Genera Atheris, Cerastes, and Proatheris and the Relative Efficacy of Antivenoms and Synthetic Enzyme-Inhibitors

The African viperid snake genera Atheris, Cerastes, and Proatheris are closely related, similar in size, but occupy extremely divergent ecological niches (arboreal in tropical rainforests, fossorial in deserts, and swamp-dwelling, respectively). Their venoms have not previously been subjected to com...

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Autores principales: Chowdhury, Abhinandan, Lewin, Matthew R., Carter, Rebecca, Soria, Raul, Aldridge, Matt, Fry, Bryan G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788330/
https://www.ncbi.nlm.nih.gov/pubmed/36548733
http://dx.doi.org/10.3390/toxins14120836
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author Chowdhury, Abhinandan
Lewin, Matthew R.
Carter, Rebecca
Soria, Raul
Aldridge, Matt
Fry, Bryan G.
author_facet Chowdhury, Abhinandan
Lewin, Matthew R.
Carter, Rebecca
Soria, Raul
Aldridge, Matt
Fry, Bryan G.
author_sort Chowdhury, Abhinandan
collection PubMed
description The African viperid snake genera Atheris, Cerastes, and Proatheris are closely related, similar in size, but occupy extremely divergent ecological niches (arboreal in tropical rainforests, fossorial in deserts, and swamp-dwelling, respectively). Their venoms have not previously been subjected to comparative analyses for their action upon the coagulation of blood, most notably with significant data deficiencies from Atheris and Proatheris. In contrast, the closely related genus Echis is well-documented as capable of producing potent procoagulant effects. In light of this, we set out to compare the coagulotoxic actions of Atheris ceratophora, A. chlorechis, A. desaixi, A. nitschei, A. squamigera, C. cerastes, C. cerastes gasperettii, C. vipera, and Proatheris superciliaris and explore potential pharmacological interventions to reestablish normal blood coagulation. All venoms displayed extremely potent procoagulant effects, over twice as fast as the most potent Echis reported to date. Although Cerastes is used in the immunising mixture of two different regionally available antivenoms (Inoserp-MENA with C. cerastes, C. cerastes gasperettii, C. vipera and Saudi Arabian polyvalent with C. cerastes), none of the other species in this study are included in the immunising mixture of any antivenom. Notably, all the Cerastes species were only neutralised by the Inoserp-MENA antivenom. C. cerastes venom was not neutralised well by the Saudi Arabian antivenom, with the low levels of recognition for any of the Cerastes venoms suggesting a strong regional variation in the venom of this species, as the C. cerastes venom tested was of African (Tunisian) origin versus Saudi locality used in that antivenom’s production. The other antivenoms (Micropharm EchiTAbG, ICP EchiTAb-Plus-ICP, Inosan Inoserp Pan-Africa, Premium Serums PANAF Sub-Sahara Africa, South African Vaccine Producers Echis, South African Vaccine Producers Polyvalent) all displayed trivial-to-no ability to neutralise the procoagulant toxicity of any of the Atheris, Cerastes, or Proatheris venoms. Comparative testing of the enzyme inhibitors DMPS, marimastat, and prinomastat, revealed a very potent neutralising capacity of marimastat, with prinomastat showing lower but still significant potency at the same molar concentration, while a 5× molar concentration of DMPS had no apparent effect on procoagulant venom effects normalized by the other inhibitors. These results and methods contribute to the body of knowledge of potential clinical effects and data necessary for evidence-based advancement of clinical management strategies.
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spelling pubmed-97883302022-12-24 Extreme Procoagulant Potency in Human Plasma of Venoms from the African Viperid Genera Atheris, Cerastes, and Proatheris and the Relative Efficacy of Antivenoms and Synthetic Enzyme-Inhibitors Chowdhury, Abhinandan Lewin, Matthew R. Carter, Rebecca Soria, Raul Aldridge, Matt Fry, Bryan G. Toxins (Basel) Article The African viperid snake genera Atheris, Cerastes, and Proatheris are closely related, similar in size, but occupy extremely divergent ecological niches (arboreal in tropical rainforests, fossorial in deserts, and swamp-dwelling, respectively). Their venoms have not previously been subjected to comparative analyses for their action upon the coagulation of blood, most notably with significant data deficiencies from Atheris and Proatheris. In contrast, the closely related genus Echis is well-documented as capable of producing potent procoagulant effects. In light of this, we set out to compare the coagulotoxic actions of Atheris ceratophora, A. chlorechis, A. desaixi, A. nitschei, A. squamigera, C. cerastes, C. cerastes gasperettii, C. vipera, and Proatheris superciliaris and explore potential pharmacological interventions to reestablish normal blood coagulation. All venoms displayed extremely potent procoagulant effects, over twice as fast as the most potent Echis reported to date. Although Cerastes is used in the immunising mixture of two different regionally available antivenoms (Inoserp-MENA with C. cerastes, C. cerastes gasperettii, C. vipera and Saudi Arabian polyvalent with C. cerastes), none of the other species in this study are included in the immunising mixture of any antivenom. Notably, all the Cerastes species were only neutralised by the Inoserp-MENA antivenom. C. cerastes venom was not neutralised well by the Saudi Arabian antivenom, with the low levels of recognition for any of the Cerastes venoms suggesting a strong regional variation in the venom of this species, as the C. cerastes venom tested was of African (Tunisian) origin versus Saudi locality used in that antivenom’s production. The other antivenoms (Micropharm EchiTAbG, ICP EchiTAb-Plus-ICP, Inosan Inoserp Pan-Africa, Premium Serums PANAF Sub-Sahara Africa, South African Vaccine Producers Echis, South African Vaccine Producers Polyvalent) all displayed trivial-to-no ability to neutralise the procoagulant toxicity of any of the Atheris, Cerastes, or Proatheris venoms. Comparative testing of the enzyme inhibitors DMPS, marimastat, and prinomastat, revealed a very potent neutralising capacity of marimastat, with prinomastat showing lower but still significant potency at the same molar concentration, while a 5× molar concentration of DMPS had no apparent effect on procoagulant venom effects normalized by the other inhibitors. These results and methods contribute to the body of knowledge of potential clinical effects and data necessary for evidence-based advancement of clinical management strategies. MDPI 2022-12-01 /pmc/articles/PMC9788330/ /pubmed/36548733 http://dx.doi.org/10.3390/toxins14120836 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chowdhury, Abhinandan
Lewin, Matthew R.
Carter, Rebecca
Soria, Raul
Aldridge, Matt
Fry, Bryan G.
Extreme Procoagulant Potency in Human Plasma of Venoms from the African Viperid Genera Atheris, Cerastes, and Proatheris and the Relative Efficacy of Antivenoms and Synthetic Enzyme-Inhibitors
title Extreme Procoagulant Potency in Human Plasma of Venoms from the African Viperid Genera Atheris, Cerastes, and Proatheris and the Relative Efficacy of Antivenoms and Synthetic Enzyme-Inhibitors
title_full Extreme Procoagulant Potency in Human Plasma of Venoms from the African Viperid Genera Atheris, Cerastes, and Proatheris and the Relative Efficacy of Antivenoms and Synthetic Enzyme-Inhibitors
title_fullStr Extreme Procoagulant Potency in Human Plasma of Venoms from the African Viperid Genera Atheris, Cerastes, and Proatheris and the Relative Efficacy of Antivenoms and Synthetic Enzyme-Inhibitors
title_full_unstemmed Extreme Procoagulant Potency in Human Plasma of Venoms from the African Viperid Genera Atheris, Cerastes, and Proatheris and the Relative Efficacy of Antivenoms and Synthetic Enzyme-Inhibitors
title_short Extreme Procoagulant Potency in Human Plasma of Venoms from the African Viperid Genera Atheris, Cerastes, and Proatheris and the Relative Efficacy of Antivenoms and Synthetic Enzyme-Inhibitors
title_sort extreme procoagulant potency in human plasma of venoms from the african viperid genera atheris, cerastes, and proatheris and the relative efficacy of antivenoms and synthetic enzyme-inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788330/
https://www.ncbi.nlm.nih.gov/pubmed/36548733
http://dx.doi.org/10.3390/toxins14120836
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