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, Bertos, Antonio R., Sierra-Ramírez, Arantzazu, del Moral-Salmoral, Javier, Merino, Javier, de Avila, Ana I., Olague, Cristina, Rodríguez Hernández, María A., Fernández-Marcos, Pablo José, von Kobbe, Cayetano
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/180723
Acceso en línea:https://hdl.handle.net/11441/180723
https://doi.org/10.1111/acel.13771
Access Level:acceso abierto
Palabra clave:Cellular senescence
COVID-19
SARS-CoV- 2
Senolytics
Survival
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spelling Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in micePastor-Fernández, AndrésBertos, Antonio R.Sierra-Ramírez, Arantzazudel Moral-Salmoral, JavierMerino, Javierde Avila, Ana I.Olague, CristinaRodríguez Hernández, María A.Fernández-Marcos, Pablo Josévon Kobbe, CayetanoCellular senescenceCOVID-19SARS-CoV- 2SenolyticsSurvivalThe 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.WileyBiología CelularInstituto de Salud Carlos IIIAsociación Española Contra el CáncerMinisterio de Ciencia e Innovación (MICIN). EspañaEuropean Union (UE)Consejo Superior de Investigaciones Científicas (CSIC)European Commission (EC)2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/180723https://doi.org/10.1111/acel.13771reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésAging Cell, 22 (3), e13771.COV20-00755COV20-00792PRDMA18011PASTLABAE18008FERNSAF2017-85766- RPID2020-114077RB- I00RYC-2017- 22335PID2020-113888RB- I00COVTRAVI-19- CMUCSIC-COV19- 014EU2020/2094https://doi.org/10.1111/acel.13771info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1807232026-06-17T12:51:07Z
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
Cellular senescence
COVID-19
SARS-CoV- 2
Senolytics
Survival
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
Bertos, Antonio R.
Sierra-Ramírez, Arantzazu
del Moral-Salmoral, Javier
Merino, Javier
de Avila, Ana I.
Olague, Cristina
Rodríguez Hernández, María A.
Fernández-Marcos, Pablo José
von Kobbe, Cayetano
author Pastor-Fernández, Andrés
author_facet Pastor-Fernández, Andrés
Bertos, Antonio R.
Sierra-Ramírez, Arantzazu
del Moral-Salmoral, Javier
Merino, Javier
de Avila, Ana I.
Olague, Cristina
Rodríguez Hernández, María A.
Fernández-Marcos, Pablo José
von Kobbe, Cayetano
author_role author
author2 Bertos, Antonio R.
Sierra-Ramírez, Arantzazu
del Moral-Salmoral, Javier
Merino, Javier
de Avila, Ana I.
Olague, Cristina
Rodríguez Hernández, María A.
Fernández-Marcos, Pablo José
von Kobbe, Cayetano
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Biología Celular
Instituto de Salud Carlos III
Asociación Española Contra el Cáncer
Ministerio de Ciencia e Innovación (MICIN). España
European Union (UE)
Consejo Superior de Investigaciones Científicas (CSIC)
European Commission (EC)
dc.subject.none.fl_str_mv Cellular senescence
COVID-19
SARS-CoV- 2
Senolytics
Survival
topic Cellular senescence
COVID-19
SARS-CoV- 2
Senolytics
Survival
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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/180723
https://doi.org/10.1111/acel.13771
url https://hdl.handle.net/11441/180723
https://doi.org/10.1111/acel.13771
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Aging Cell, 22 (3), e13771.
COV20-00755
COV20-00792
PRDMA18011PAST
LABAE18008FERN
SAF2017-85766- R
PID2020-114077RB- I00
RYC-2017- 22335
PID2020-113888RB- I00
COVTRAVI-19- CMU
CSIC-COV19- 014
EU2020/2094
https://doi.org/10.1111/acel.13771
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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