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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Detalles Bibliográficos
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
Descripción
Sumario: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.