The SARS-CoV-2 spike protein binds and modulates estrogen receptors

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 hum...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/192288
Acceso en línea:https://hdl.handle.net/2445/192288
Access Level:acceso abierto
Palabra clave:SARS-CoV-2
Pandèmia de COVID-19, 2020-
Fixació de proteïnes
COVID-19 Pandemic, 2020-
Protein binding
Descripción
Sumario: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 alpha (ER alpha). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 sub-unit. In cultured cells, S DNA transfection increased ER alpha cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2-infected hamsters localized lung pathology with increased ER alpha lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ER alpha and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ER alpha interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology.

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