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, Ávila, Ana Isabel de, Olagüe, Cristina, Villares, Ricardo, González-Aseguinolaza, Gloria, Rodríguez, María Ángeles, Fresno, Manuel, Gironés, Nuria, Bustos, Matilde, Smerdou, Cristian, Fernández-Marcos, Pablo José, Von Kobbe, Cayetano
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/308426
Acceso en línea:http://hdl.handle.net/10261/308426
https://api.elsevier.com/content/abstract/scopus_id/85147271700
Access Level:acceso abierto
Palabra clave:COVID-19
SARS-CoV-2
Cellular senescence
Senolytics
Survival
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oai_identifier_str oai:digital.csic.es:10261/308426
network_acronym_str ES
network_name_str España
repository_id_str
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
COVID-19
SARS-CoV-2
Cellular senescence
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
Ávila, Ana Isabel de
Olagüe, Cristina
Villares, Ricardo
González-Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
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
Ávila, Ana Isabel de
Olagüe, Cristina
Villares, Ricardo
González-Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
Fernández-Marcos, Pablo José
Von Kobbe, Cayetano
author_role author
author2 Bertos, Antonio R
Sierra-Ramírez, Arantzazu
Del Moral-Salmoral, Javier
Merino, Javier
Ávila, Ana Isabel de
Olagüe, Cristina
Villares, Ricardo
González-Aseguinolaza, Gloria
Rodríguez, María Ángeles
Fresno, Manuel
Gironés, Nuria
Bustos, Matilde
Smerdou, Cristian
Fernández-Marcos, Pablo José
Von Kobbe, Cayetano
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Apadrina la Ciencia
Fundación Científica Asociación Española Contra el Cáncer
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Ciencia e Innovación (España)
European Commission
Consejo Superior de Investigaciones Científicas (España)
CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM)
Pastor-Fernández, Andrés [0000-0002-8060-073X]
Fernández-Marcos, Pablo José [0000-0003-3515-4125]
Kobbe, Cayetano von [0000-0003-3895-3790]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv COVID-19
SARS-CoV-2
Cellular senescence
Senolytics
Survival
topic COVID-19
SARS-CoV-2
Cellular senescence
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
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
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status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/308426
https://api.elsevier.com/content/abstract/scopus_id/85147271700
url http://hdl.handle.net/10261/308426
https://api.elsevier.com/content/abstract/scopus_id/85147271700
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language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI//RYC-2017-22335
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113888RB-I00
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1111/acel.13771
https://doi.org/10.1111/acel.13771
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dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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spelling Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in micePastor-Fernández, AndrésBertos, Antonio RSierra-Ramírez, ArantzazuDel Moral-Salmoral, JavierMerino, JavierÁvila, Ana Isabel deOlagüe, CristinaVillares, RicardoGonzález-Aseguinolaza, GloriaRodríguez, María ÁngelesFresno, ManuelGironés, NuriaBustos, MatildeSmerdou, CristianFernández-Marcos, Pablo JoséVon Kobbe, CayetanoCOVID-19SARS-CoV-2Cellular senescenceSenolyticsSurvivalThe 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.This work was supported by grants from the Instituto de Salud Carlos III (ISCIII), COV20-00755 (C.V.K.) and COV20-00792 (M.B., M.A.R.), Apadrina la Ciencia (C.S., C.O., G.G.A.), the AECC Scientific Foundation, PRDMA18011PAST, SIRTBIO- LABAE18008FERN (P.J.F.M., A.P., A.S.R.), the RETOS projects Programme of Ministerio de Ciencia e Innovación (MICINN), SAF2017-85766-R and PID2020-114077RB-I00 (P.J.F.M., A.P., A.S.R.), Ramon y Cajal Award from MICINN, RYC-2017-22335 (P.J.F.M., A.P., A.S.R.), Proyecto REACT from REACT/European Union/FEDER, COVTRAVI-19-CM U (J.M.S., M.F., N.G.), grant from Consejo Superior de Investigaciones Científicas (CSIC), CSIC-COV19-014 (A.I.d.Á), PID2020-113888RB-I00 from MICINN (A.I.d.Á), and the European Commission–Next Generation EU (regulation EU 2020/2094), through the CSIC's Global Health Platform (PTI+ Global Health) (A.I.d.Á). The RT–qPCR reactions were provided by the Genomics and NGS Core Facility (GENGS) at the Centro de Biología Molecular Severo Ochoa (CBMSO, CSIC-UAM) Madrid, Spain, which obtains general funding from both institutions. The GENGS facility is part of the PTI+ Global Health (CSIC) (http://www.cbm.uam.es/genomica).Peer reviewedJohn Wiley & SonsInstituto de Salud Carlos IIIApadrina la CienciaFundación Científica Asociación Española Contra el CáncerAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Ministerio de Ciencia e Innovación (España)European CommissionConsejo Superior de Investigaciones Científicas (España)CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM)Pastor-Fernández, Andrés [0000-0002-8060-073X]Fernández-Marcos, Pablo José [0000-0003-3515-4125]Kobbe, Cayetano von [0000-0003-3895-3790]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/308426https://api.elsevier.com/content/abstract/scopus_id/85147271700reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-85766-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114077RB-I00info:eu-repo/grantAgreement/AEI//RYC-2017-22335info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113888RB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1111/acel.13771https://doi.org/10.1111/acel.13771Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3084262026-05-22T06:33:51Z
score 15.811543

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