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Title: | The SARS-CoV-2 spike protein binds and modulates estrogen receptors | Authors: | Solis, Oscar Beccari, Andrea R Iaconis, Daniela Talarico, Carmine Ruiz-Bedoya, Camilo A Nwachukwu, Jerome C Cimini, Annamaria Castelli, Vanessa Bertini, Riccardo Montopoli, Monica Cocetta, Veronica Borocci, Stefano Prandi, Ingrid G Flavahan, Kelly Bahr, Melissa Napiorkowski, Anna Chillemi, Giovanni Ooka, Masato Yang, Xiaoping Zhang, Shiliang Xia, Menghang Zheng, Wei Bonaventura, Jordi Pomper, Martin G Hooper, Jody E Morales, Marisela Rosenberg, Avi Z Nettles, Kendall W Jain, Sanjay K Allegretti, Marcello Michaelides, Michael |
Journal: | SCIENCE ADVANCES | Issue Date: | 2022 | Abstract: | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 as its primary infection mechanism. Interactions between S and endogenous proteins occur after infection but are not well understood. We profiled binding of S against >9000 human proteins and found an interaction between S and human estrogen receptor α (ERα). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2-infected hamsters localized lung pathology with increased ERα lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ERα and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ERα interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology. |
URI: | http://hdl.handle.net/2067/48736 | ISSN: | 23752548 | DOI: | 10.1126/sciadv.add4150 | Rights: | Attribution-NonCommercial-NoDerivatives 4.0 International |
Appears in Collections: | A1. Articolo in rivista |
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