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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
Issue Date: 2022
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.
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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