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‐...

Full description

Saved in:
Bibliographic Details
Published in:Aging cell 2023-03, Vol.22 (3), p.e13771-n/a
Main Authors: Pastor‐Fernández, Andrés, Bertos, Antonio R., Sierra‐Ramírez, Arantzazu, Moral‐Salmoral, Javier, Merino, Javier, 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, Kobbe, Cayetano
Format: Article
Language:English
Subjects:
Animal models
Animals
Cellular Senescence
Complications
Coronaviruses
COVID-19
Dasatinib - pharmacology
Dasatinib - therapeutic use
Disease prevention
Dyspnea
Experiments
Humans
Immune clearance
Immune response
Immunosuppressive agents
Infections
Inflammation
Lungs
Mice
Mortality
Pandemics
Quercetin
Quercetin - pharmacology
Quercetin - therapeutic use
SARS-CoV-2
senolytics
Senotherapeutics
Severe acute respiratory syndrome coronavirus 2
survival
Viral infections
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
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. New treatments are necessary to reduce the social impact of COVID‐19. Using the murine model K18‐hACE2, we demonstrated that senolytics (D/Q) reduced SARS‐CoV‐2‐related mortality, delayed its onset, and reduced the number of other clinical symptoms.
ISSN:1474-9718
1474-9726
1474-9726
DOI:10.1111/acel.13771