Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice

The enormous societal impact of the ongoing COVID‐19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro‐inflammatory immune response against SARS‐CoV‐...

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Autores: Pastor Fernández, Andrés, Sierra Ramírez, Arantzazu, del Moral Salmoral, Javier, Merino, Javier, de Ávila, Ana I., Olagüe, Cristina, Villares, Ricardo, González Aseguinolaza, Gloria, Rodríguez, María Ángeles, Fresno, Manuel, Gironés, Nuria, Bustos, Matilde, Smerdou, Cristian, Fernandez Marcos, Pablo Jose, von Kobbe, Cayetano, Rodríguez Bertos, Antonio Manuel
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/107558
Acceso en línea:https://hdl.handle.net/20.500.14352/107558
Access Level:acceso abierto
Palabra clave:636.09
cellular senescence
COVID-19
SARS-CoV-2
senolytics
survival
Veterinaria
3109 Ciencias Veterinarias
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spelling Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in micePastor Fernández, AndrésSierra Ramírez, Arantzazudel Moral Salmoral, JavierMerino, Javierde Ávila, Ana I.Olagüe, CristinaVillares, RicardoGonzález Aseguinolaza, GloriaRodríguez, María ÁngelesFresno, ManuelGironés, NuriaBustos, MatildeSmerdou, CristianFernandez Marcos, Pablo Josevon Kobbe, CayetanoRodríguez Bertos, Antonio Manuel636.09cellular senescenceCOVID-19SARS-CoV-2senolyticssurvivalVeterinaria3109 Ciencias VeterinariasThe enormous societal impact of the ongoing COVID‐19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro‐inflammatory immune response against SARS‐CoV‐2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID‐19 in some cases. Using the established COVID‐19 murine model K18‐hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS‐CoV‐2‐related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS‐CoV‐2 may be related to the post‐COVID‐19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID‐19, and make D/Q a new and promising therapeutic tool.WileyUniversidad Complutense de Madrid20232023-01-2620232023-01-26journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/107558reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PID2020-114077RB-I00 CARACTERIZACION DE LOS MECANISMOS MOLECULARES DEL AYUNO DE CORTA DURACION CONTRA EL CANCER Y EL SINDROME METABOLICO.open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1075582026-06-02T12:44:21Z
dc.title.none.fl_str_mv Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
spellingShingle Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
Pastor Fernández, Andrés
636.09
cellular senescence
COVID-19
SARS-CoV-2
senolytics
survival
Veterinaria
3109 Ciencias Veterinarias
title_short Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_full Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_fullStr Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_full_unstemmed Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
title_sort Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV‐2‐related mortality in mice
dc.creator.none.fl_str_mv Pastor Fernández, Andrés
Sierra Ramírez, Arantzazu
del Moral Salmoral, Javier
Merino, Javier
de Ávila, Ana I.
Olagüe, Cristina
Villares, Ricardo
González Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
Fernandez Marcos, Pablo Jose
von Kobbe, Cayetano
Rodríguez Bertos, Antonio Manuel
author Pastor Fernández, Andrés
author_facet Pastor Fernández, Andrés
Sierra Ramírez, Arantzazu
del Moral Salmoral, Javier
Merino, Javier
de Ávila, Ana I.
Olagüe, Cristina
Villares, Ricardo
González Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
Fernandez Marcos, Pablo Jose
von Kobbe, Cayetano
Rodríguez Bertos, Antonio Manuel
author_role author
author2 Sierra Ramírez, Arantzazu
del Moral Salmoral, Javier
Merino, Javier
de Ávila, Ana I.
Olagüe, Cristina
Villares, Ricardo
González Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
Fernandez Marcos, Pablo Jose
von Kobbe, Cayetano
Rodríguez Bertos, Antonio Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 636.09
cellular senescence
COVID-19
SARS-CoV-2
senolytics
survival
Veterinaria
3109 Ciencias Veterinarias
topic 636.09
cellular senescence
COVID-19
SARS-CoV-2
senolytics
survival
Veterinaria
3109 Ciencias Veterinarias
description The enormous societal impact of the ongoing COVID‐19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro‐inflammatory immune response against SARS‐CoV‐2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID‐19 in some cases. Using the established COVID‐19 murine model K18‐hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS‐CoV‐2‐related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS‐CoV‐2 may be related to the post‐COVID‐19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID‐19, and make D/Q a new and promising therapeutic tool.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-26
2023
2023-01-26
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/107558
url https://hdl.handle.net/20.500.14352/107558
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 PID2020-114077RB-I00 CARACTERIZACION DE LOS MECANISMOS MOLECULARES DEL AYUNO DE CORTA DURACION CONTRA EL CANCER Y EL SINDROME METABOLICO.
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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