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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/192288
The SARS-CoV-2 spike protein binds and modulates estrogen receptors
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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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SOLIS, Oscar, et al. The SARS-CoV-2 spike protein binds and modulates estrogen receptors. Science Advances. 2022. Vol. 8, num. 48, pags. eadd4150. ISSN 2375-2548. [consulted: 16 of June of 2026]. Available at: https://hdl.handle.net/2445/192288