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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Bibliographic Details
Authors: 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
Format: article
Status:Published version
Publication Date:2023
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/308426
Online Access:http://hdl.handle.net/10261/308426
https://api.elsevier.com/content/abstract/scopus_id/85147271700
Access Level:Open access
Keyword:COVID-19
SARS-CoV-2
Cellular senescence
Senolytics
Survival
Description
Summary: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.