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

Autores: Pastor-Fernández, A.; Bertos, A. R.; Sierra-Ramírez, A.; del Moral-Salmoral, J.; Merino, J.; de Ávila, A. I.; Olague Micheltorena, María Cristina; Villares, R.; González Aseguinolaza, Gloria; Rodríguez, M. Á.; Fresno, M.; Gironés, N.; Bustos, M.; Smerdou Picazo, Cristian; Fernández-Marcos, P. J.; von Kobbe, C. (Autor de correspondencia)
Título de la revista: AGING CELL
ISSN: 1474-9718
Volumen: 22
Número: 3
Páginas: e13771
Fecha de publicación: 2023
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.