Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity

Autores
López, Gisela Lumila; Nielsen, Sarah A.; Nielsen, Vance G.; Fusco, Luciano Sebastian
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Bothrops species are responsible for the majority of envenomations in Argentina. In particular, Bothrops diporus is among the main species responsible for the majority of envenomations in Argentina and causes significant injury and coagulopathy. Given the significance of this venom, the authors sought to define the toxin responsible for coagulopathy with specialized spectrophotometric and thromboelastographic methods. Utilizing clotting time, spectrophotometry, and thromboelastography, it was determined that B. diporus venom has potent, procoagulant activity in human plasma and buffer milieu. Calcium-dependent and -independent activities consistent with serine protease activity were identified. The activity included both thrombin-generating and thrombin-like enzymatic activity. The venom cleaved the serine protease-specific chromogenic substrate β-Ala-Gly-Arg-p-nitroanilide diacetate, and its activity was inhibited in plasma by antithrombin after addition of heparin. Further, venom exposed in isolation to RuCl3, a known inhibitor of serine protease-containing venoms, demonstrated decreased activity in human plasma. In conclusion, the present study contributes to a better understanding of B. diporus venom and may have implications for the rational design of inhibitors, antivenom formulations, or preclinical models to study venom-induced coagulopathies.
Fil: López, Gisela Lumila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Nielsen, Sarah A.. University of Arizona; Estados Unidos
Fil: Nielsen, Vance G.. University of Arizona; Estados Unidos
Fil: Fusco, Luciano Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Materia
Bothrops species
venom
serine protease
coagulation time
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/276808
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/276808
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease ActivityLópez, Gisela LumilaNielsen, Sarah A.Nielsen, Vance G.Fusco, Luciano SebastianBothrops speciesvenomserine proteasecoagulation timehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Bothrops species are responsible for the majority of envenomations in Argentina. In particular, Bothrops diporus is among the main species responsible for the majority of envenomations in Argentina and causes significant injury and coagulopathy. Given the significance of this venom, the authors sought to define the toxin responsible for coagulopathy with specialized spectrophotometric and thromboelastographic methods. Utilizing clotting time, spectrophotometry, and thromboelastography, it was determined that B. diporus venom has potent, procoagulant activity in human plasma and buffer milieu. Calcium-dependent and -independent activities consistent with serine protease activity were identified. The activity included both thrombin-generating and thrombin-like enzymatic activity. The venom cleaved the serine protease-specific chromogenic substrate β-Ala-Gly-Arg-p-nitroanilide diacetate, and its activity was inhibited in plasma by antithrombin after addition of heparin. Further, venom exposed in isolation to RuCl3, a known inhibitor of serine protease-containing venoms, demonstrated decreased activity in human plasma. In conclusion, the present study contributes to a better understanding of B. diporus venom and may have implications for the rational design of inhibitors, antivenom formulations, or preclinical models to study venom-induced coagulopathies.Fil: López, Gisela Lumila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Nielsen, Sarah A.. University of Arizona; Estados UnidosFil: Nielsen, Vance G.. University of Arizona; Estados UnidosFil: Fusco, Luciano Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaMolecular Diversity Preservation International2025-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/276808López, Gisela Lumila; Nielsen, Sarah A.; Nielsen, Vance G.; Fusco, Luciano Sebastian; Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 19; 9-2025; 1-161422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/26/19/9496info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms26199496info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:52:52Zoai:ri.conicet.gov.ar:11336/276808instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-12-23 13:52:52.943CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity
title Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity
spellingShingle Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity
López, Gisela Lumila
Bothrops species
venom
serine protease
coagulation time
title_short Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity
title_full Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity
title_fullStr Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity
title_full_unstemmed Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity
title_sort Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity
dc.creator.none.fl_str_mv López, Gisela Lumila
Nielsen, Sarah A.
Nielsen, Vance G.
Fusco, Luciano Sebastian
author López, Gisela Lumila
author_facet López, Gisela Lumila
Nielsen, Sarah A.
Nielsen, Vance G.
Fusco, Luciano Sebastian
author_role author
author2 Nielsen, Sarah A.
Nielsen, Vance G.
Fusco, Luciano Sebastian
author2_role author
author
author
dc.subject.none.fl_str_mv Bothrops species
venom
serine protease
coagulation time
topic Bothrops species
venom
serine protease
coagulation time
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Bothrops species are responsible for the majority of envenomations in Argentina. In particular, Bothrops diporus is among the main species responsible for the majority of envenomations in Argentina and causes significant injury and coagulopathy. Given the significance of this venom, the authors sought to define the toxin responsible for coagulopathy with specialized spectrophotometric and thromboelastographic methods. Utilizing clotting time, spectrophotometry, and thromboelastography, it was determined that B. diporus venom has potent, procoagulant activity in human plasma and buffer milieu. Calcium-dependent and -independent activities consistent with serine protease activity were identified. The activity included both thrombin-generating and thrombin-like enzymatic activity. The venom cleaved the serine protease-specific chromogenic substrate β-Ala-Gly-Arg-p-nitroanilide diacetate, and its activity was inhibited in plasma by antithrombin after addition of heparin. Further, venom exposed in isolation to RuCl3, a known inhibitor of serine protease-containing venoms, demonstrated decreased activity in human plasma. In conclusion, the present study contributes to a better understanding of B. diporus venom and may have implications for the rational design of inhibitors, antivenom formulations, or preclinical models to study venom-induced coagulopathies.
Fil: López, Gisela Lumila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Nielsen, Sarah A.. University of Arizona; Estados Unidos
Fil: Nielsen, Vance G.. University of Arizona; Estados Unidos
Fil: Fusco, Luciano Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
description Bothrops species are responsible for the majority of envenomations in Argentina. In particular, Bothrops diporus is among the main species responsible for the majority of envenomations in Argentina and causes significant injury and coagulopathy. Given the significance of this venom, the authors sought to define the toxin responsible for coagulopathy with specialized spectrophotometric and thromboelastographic methods. Utilizing clotting time, spectrophotometry, and thromboelastography, it was determined that B. diporus venom has potent, procoagulant activity in human plasma and buffer milieu. Calcium-dependent and -independent activities consistent with serine protease activity were identified. The activity included both thrombin-generating and thrombin-like enzymatic activity. The venom cleaved the serine protease-specific chromogenic substrate β-Ala-Gly-Arg-p-nitroanilide diacetate, and its activity was inhibited in plasma by antithrombin after addition of heparin. Further, venom exposed in isolation to RuCl3, a known inhibitor of serine protease-containing venoms, demonstrated decreased activity in human plasma. In conclusion, the present study contributes to a better understanding of B. diporus venom and may have implications for the rational design of inhibitors, antivenom formulations, or preclinical models to study venom-induced coagulopathies.
publishDate 2025
dc.date.none.fl_str_mv 2025-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/276808
López, Gisela Lumila; Nielsen, Sarah A.; Nielsen, Vance G.; Fusco, Luciano Sebastian; Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 19; 9-2025; 1-16
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/276808
identifier_str_mv López, Gisela Lumila; Nielsen, Sarah A.; Nielsen, Vance G.; Fusco, Luciano Sebastian; Procoagulant Effects of Bothrops diporus Venom: Kinetic Modeling and Role of Serine Protease Activity; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 19; 9-2025; 1-16
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/26/19/9496
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms26199496
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.952241

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