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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
Pastor-Fernández et al., Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2 related mortality in mice, Aging Cell, doi:10.1111/acel.13771
Jan 2023   Source   PDF  
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K18-hACE2 mouse study showing reduced COVID-19 severity with quercetin and dasatinib, for both prophylaxis and early treatment.
Pastor-Fernández et al., 26 Jan 2023, Spain, peer-reviewed, survey, 16 authors.
Contact: cvonkobbe@cbm.csic.es.
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Abstract: | Revised: 7 December 2022 | Accepted: 20 December 2022 DOI: 10.1111/acel.13771 RESEARCH ARTICLE Treatment with the senolytics dasatinib/quercetin reduces SARS-­CoV-­2-­related mortality in mice Andrés Pastor-­Fernández1 | Antonio R. Bertos2 | Arantzazu Sierra-­Ramírez1 | Javier del Moral-­Salmoral3,4 | Javier Merino3,4 | Ana I. de Ávila4,5 | Cristina Olagüe6 | Ricardo Villares7 | Gloria González-­Aseguinolaza6 | María Ángeles Rodríguez8 | Manuel Fresno3,4 | Nuria Gironés3,4 | Matilde Bustos8 | Cristian Smerdou6 | Pablo Jose Fernandez-­Marcos1 | Cayetano von Kobbe4 1 Metabolic Syndrome Group-­BIOPROMET, Madrid Institute for Advanced Studies-­IMDEA Food, CEI UAM+CSIC, Madrid, Spain 2 Department of Internal Medicine and Surgical Animal, Faculty of Veterinary/VISAVET Centre, Complutense University of Madrid, Madrid, Spain 3 Departamento de Biología Molecular, Universidad Autónoma de Madrid (UAM), Madrid, Spain 4 Centro de Biología Molecular Severo Ochoa (CSIC-­UAM), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain 5 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain 6 Division of Gene Therapy and Regulation of Gene Expression, CIMA Universidad de Navarra, Pamplona, Spain 7 Centro Nacional de Biotecnología (CNB-­C SIC), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain 8 Institute of Biomedicine of Seville (IBiS), Spanish National Research Council (CSIC), University of Seville, Virgen del Rocio University Hospital, Seville, Spain Correspondence Cayetano von Kobbe, Centro de Biología Molecular Severo Ochoa (CSIC-­UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, Madrid E28049, Spain. Email: cvonkobbe@cbm.csic.es Funding information Instituto de Salud Carlos III, Grant/ Award Number: COV20-­0 0755 and COV20-­0 0792; AECC Scientific Foundation, Grant/Award Number: PRDMA18011PAST; SIRTBIO, Grant/ Award Number: LABAE18008FERN; MICINN, Grant/Award Number: SAF2017-­ 85766-­R , PID2020-­114077RB-­I 00, RYC-­ 2017-­22335 and PID2020-­113888RB-­I 00; REACT/European Union/FEDER, Grant/ Award Number: COVTRAVI-­19-­CMU; CSIC, Grant/Award Number: CSIC-­ COV19-­014; European Commission-­ NextGeneration EU, Grant/Award Number: EU2020/2094; PTI Salud Global CSIC; Apadrina la Ciencia 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. KEYWORDS cellular senescence, COVID-­19, SARS-­CoV-­2, senolytics,..
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