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The SARS-CoV-2 spike protein binds and modulates estrogen receptors
Solis, Oscar Beccari, Andrea R. Iaconis, Daniela Talarico, Carmine Ruiz-Bedoya, Camilo A. Nwachukwu, Jerome C. Castelli, Vanessa Bertini, Riccardo Montopoli, Monica
Solis, Oscar
Beccari, Andrea R.
Iaconis, Daniela
Talarico, Carmine
Ruiz-Bedoya, Camilo A.
Nwachukwu, Jerome C.
Castelli, Vanessa
Bertini, Riccardo
Montopoli, Monica
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Journal article
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2022-11-30
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Biology
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http://dx.doi.org/10.1126/sciadv.add4150
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.
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Oscar Solis et al. ,The SARS-CoV-2 spike protein binds and modulates estrogen receptors.Sci. Adv.8,eadd4150(2022).DOI:10.1126/sciadv.add4150
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American Association for the Advancement of Science (AAAS)
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Science Advances, Vol. 8, Iss. 48
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