1. Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice.
- Author
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Pastor-Fernández A, Bertos AR, Sierra-Ramírez A, Del Moral-Salmoral J, Merino J, de Ávila AI, Olagüe C, Villares R, González-Aseguinolaza G, Rodríguez MÁ, Fresno M, Gironés N, Bustos M, Smerdou C, Fernandez-Marcos PJ, and von Kobbe C
- Subjects
- Mice, Humans, Animals, Dasatinib pharmacology, Dasatinib therapeutic use, SARS-CoV-2, Cellular Senescence, Senotherapeutics, Pandemics, Quercetin pharmacology, Quercetin therapeutic use, COVID-19
- Abstract
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., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
- Published
- 2023
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