The SARS-CoV-2 spike protein binds and modulates estrogen receptors
Year: 2022
Type: article
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.
Source: UnitusOpen (Tuscia University)
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
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7212268466
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