Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice.
Andrés Pastor-FernándezAntonio R BertosArantzazu Sierra-RamírezJavier Del Moral-SalmoralJavier MerinoAna I de ÁvilaCristina OlagüeRicardo VillaresGloria González-AseguinolazaMaría Ángeles RodríguezManuel FresnoNuria GironésMatilde BustosCristian SmerdouPablo Jose Fernandez-MarcosCayetano von KobbePublished in: Aging cell (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.
Keyphrases
- sars cov
- induced apoptosis
- respiratory syndrome coronavirus
- cell cycle arrest
- coronavirus disease
- immune response
- type diabetes
- healthcare
- endoplasmic reticulum stress
- cardiovascular events
- cell death
- signaling pathway
- cardiovascular disease
- oxidative stress
- dendritic cells
- risk factors
- coronary artery disease
- toll like receptor
- skeletal muscle
- mesenchymal stem cells
- metabolic syndrome
- combination therapy
- pi k akt
- drug induced
- cell therapy