دورية أكاديمية
BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2
| العنوان: | BRD2 inhibition blocks SARS-CoV-2 infection by reducing transcription of the host cell receptor ACE2 |
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| المؤلفون: | Samelson, Avi, J, Tran, Quang Dinh, Robinot, Rémy, Carrau, Lucia, Rezelj, Veronica, V, Kain, Alice Mac, Chen, Merissa, Ramadoss, Gokul, N, Guo, Xiaoyan, Lim, Shion, A, Lui, Irene, Nuñez, James, K, Rockwood, Sarah, J, Wang, Jianhui, Liu, Na, Carlson-Stevermer, Jared, Oki, Jennifer, Maures, Travis, Holden, Kevin, Weissman, Jonathan, S, Wells, James, A, Conklin, Bruce, R, Tenoever, Benjamin, R, Chakrabarti, Lisa, A, Vignuzzi, Marco, Tian, Ruilin, Kampmann, Martin |
| المساهمون: | University of California San Francisco (UC San Francisco), University of California (UC), Chan Zuckerberg BioHub San Francisco, CA, Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), École Doctorale Bio Sorbonne Paris Cité Paris (ED562 - BioSPC), Université Sorbonne Paris Cité (USPC)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), NYU Langone Health New York, Gladstone Institutes San Francisco, Genentech, Inc., Genentech, Inc. San Francisco, Howard Hughes Medical Institute (HHMI), Southern University of Science and Technology (SUSTech), Synthego Redwood City, CA, Whitehead Institute, Massachusetts Institute of Technology (MIT), A.J.S. is supported by NIH grant F32AG063487. G.N.R. is supported by the NSF Graduate Research Fellowship Program (GRFP) and UCSF Discovery Fellowship. S.A.L. was a Merck Fellow of the Helen Hay Whitney Foundation. I.L. was supported by an NSF GRFP award. M.K. is a Chan Zuckerberg Biohub Investigator., We thank members of the Kampmann, Vignuzzi and Conklin laboratories, as well as V. Ramani, D. Ruggero, M. Ott and her laboratory and other members of the UCSF QBI Coronavirus Research Group (QCRG) for helpful discussions. We thank K. Leng for feedback on the manuscript. We acknowledge the Gladstone Stem Cell Core for help with cardiomyocyte production. |
| المصدر: | ISSN: 1465-7392. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; SARS-CoV-2 infection of human cells is initiated by the binding of the viral Spike protein to its cell-surface receptor ACE2. We conducted a targeted CRISPRi screen to uncover druggable pathways controlling Spike protein binding to human cells. Here we show that the protein BRD2 is required for ACE2 transcription in human lung epithelial cells and cardiomyocytes, and BRD2 inhibitors currently evaluated in clinical trials potently block endogenous ACE2 expression and SARS-CoV-2 infection of human cells, including those of human nasal epithelia. Moreover, pharmacological BRD2 inhibition with the drug ABBV-744 inhibited SARS-CoV-2 replication in Syrian hamsters. We also found that BRD2 controls transcription of several other genes induced upon SARS-CoV-2 infection, including the interferon response, which in turn regulates the antiviral response. Together, our results pinpoint BRD2 as a potent and essential regulator of the host response to SARS-CoV-2 infection and highlight the potential of BRD2 as a therapeutic target for COVID-19. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35027731; pasteur-04133563; https://pasteur.hal.science/pasteur-04133563Test; https://pasteur.hal.science/pasteur-04133563/documentTest; https://pasteur.hal.science/pasteur-04133563/file/samelson_kampmann_nihms-1759623.pdfTest; PUBMED: 35027731; PUBMEDCENTRAL: PMC8820466 |
| DOI: | 10.1038/s41556-021-00821-8 |
| الإتاحة: | https://doi.org/10.1038/s41556-021-00821-8Test https://pasteur.hal.science/pasteur-04133563Test https://pasteur.hal.science/pasteur-04133563/documentTest https://pasteur.hal.science/pasteur-04133563/file/samelson_kampmann_nihms-1759623.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.27A81EF |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41556-021-00821-8 |
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