Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice
| Autor: | 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 |
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| Přispěvatelé: | Instituto de Salud Carlos III, Apadrina la Ciencia, Fundación Científica Asociación Española Contra el Cáncer, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Ministerio de Ciencia e Innovación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM), Pastor-Fernández, Andrés, Fernández-Marcos, Pablo José, Kobbe, Cayetano von, UAM. Departamento de Biología Molecular |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Popis: | 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. This work was supported by grants from the Instituto de Salud Carlos III (ISCIII), COV20-00755 (C.V.K.) and COV20-00792 (M.B., M.A.R.), Apadrina la Ciencia (C.S., C.O., G.G.A.), the AECC Scientific Foundation, PRDMA18011PAST, SIRTBIO- LABAE18008FERN (P.J.F.M., A.P., A.S.R.), the RETOS projects Programme of Ministerio de Ciencia e Innovación (MICINN), SAF2017-85766-R and PID2020-114077RB-I00 (P.J.F.M., A.P., A.S.R.), Ramon y Cajal Award from MICINN, RYC-2017-22335 (P.J.F.M., A.P., A.S.R.), Proyecto REACT from REACT/European Union/FEDER, COVTRAVI-19-CM U (J.M.S., M.F., N.G.), grant from Consejo Superior de Investigaciones Científicas (CSIC), CSIC-COV19-014 (A.I.d.Á), PID2020-113888RB-I00 from MICINN (A.I.d.Á), and the European Commission–Next Generation EU (regulation EU 2020/2094), through the CSIC's Global Health Platform (PTI+ Global Health) (A.I.d.Á). The RT–qPCR reactions were provided by the Genomics and NGS Core Facility (GENGS) at the Centro de Biología Molecular Severo Ochoa (CBMSO, CSIC-UAM) Madrid, Spain, which obtains general funding from both institutions. The GENGS facility is part of the PTI+ Global Health (CSIC) (http://www.cbm.uam.es/genomica). |
| Databáze: | OpenAIRE |
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