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All Studies   Meta Analysis    Recent:   

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

Pastor-Fernández et al., Aging Cell, doi:10.1111/acel.13771
Jan 2023  
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Quercetin for COVID-19
23rd treatment shown to reduce risk in July 2021
 
*, now with p = 0.0031 from 11 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
K18-hACE2 mouse study showing reduced COVID-19 severity with quercetin and dasatinib, for both prophylaxis and early treatment.
Bioavailability. Quercetin has low bioavailability and studies typically use advanced formulations to improve bioavailability which may be required to reach therapeutic concentrations.
Pastor-Fernández et al., 26 Jan 2023, Spain, peer-reviewed, survey, 16 authors. Contact: cvonkobbe@cbm.csic.es.
This PaperQuercetinAll
Treatment with the senolytics dasatinib/quercetin reduces SARS‐CoV ‐2‐related mortality in mice
Andrés Pastor‐fernández, Antonio R Bertos, Arantzazu Sierra‐ramírez, Javier Del Moral‐salmoral, Javier Merino, Ana I De Ávila, Cristina Olagüe, Ricardo Villares, Gloria González‐aseguinolaza, María Ángeles Rodríguez, Manuel Fresno, Nuria Gironés, Matilde Bustos, Cristian Smerdou, Pablo Jose Fernandez‐marcos, Cayetano Von Kobbe
Aging Cell, doi:10.1111/acel.13771
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 proinflammatory 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.
| Histological processing The samples fixed in 10% neutral buffered formalin solution (Panreac Química, SLU) were mounted in synthetic paraffin with a melting point of 56 °C (Casa Álvarez Material Científico), using a Citadel 2000 Tissue Processor (Thermo Fisher Scientific), with an automatic program applying alcohols of increasing concentration and xylene substitute (Citrus Clearing Solvent, Thermo Fisher Scientific). Blocks were made in a cold plate block forming unit (Histo Star Embedding Workstation, Thermo Fisher Scientific) . Histological sections were obtained with a rotary microtome (Finesse Me+ Microtome, Thermo Fisher Scientific) at 3-4 μm thickness. A Gemini AS Automated Slide Stainer (Thermo Fisher Scientific) was used to stain the sections with hematoxylin-eosin and finally mounted using a CTM6 Coverslipper (Thermo Fisher Scientific), with a xylene-based mounting medium (ClearVue Mountant, Thermo Fisher Scientific). | Immunohistochemistry (IHC) Tissue samples were cut at 3 μm thickness, mounted on superfrost®plus slides and dried overnight. For IHC, an automated immunostaining platform was used (Autostainer Link, Dako or Ventana Discovery ULTRA; Roche). Antigen retrieval was performed with CC1 32 min, only for p21 and High pH buffer, Dako, Agilent (p19 and SARS-CoV-2 nucleocapsid); endogenous peroxidase was blocked (hydrogen peroxide at 3%) and slides were then incubated with the appropriate primary antibody as detailed: rat monoclonal anti-p21 CIP1 (291H;..
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