tetano
Editor, Senior Moderator
Sci Adv
. 2022 Dec 2;8(48):eadd4150.
doi: 10.1126/sciadv.add4150. Epub 2022 Nov 30.
The SARS-CoV-2 spike protein binds and modulates estrogen receptors
Oscar Solis[SUP] 1 [/SUP], Andrea R Beccari[SUP] 2 [/SUP], Daniela Iaconis[SUP] 2 [/SUP], Carmine Talarico[SUP] 2 [/SUP], Camilo A Ruiz-Bedoya[SUP] 3 4 5 [/SUP], Jerome C Nwachukwu[SUP] 6 [/SUP], Annamaria Cimini[SUP] 7 8 [/SUP], Vanessa Castelli[SUP] 7 [/SUP], Riccardo Bertini[SUP] 9 [/SUP], Monica Montopoli[SUP] 10 11 [/SUP], Veronica Cocetta[SUP] 10 [/SUP], Stefano Borocci[SUP] 12 [/SUP], Ingrid G Prandi[SUP] 12 [/SUP], Kelly Flavahan[SUP] 3 4 5 [/SUP], Melissa Bahr[SUP] 3 4 5 [/SUP], Anna Napiorkowski[SUP] 3 4 5 [/SUP], Giovanni Chillemi[SUP] 12 [/SUP], Masato Ooka[SUP] 13 [/SUP], Xiaoping Yang[SUP] 14 [/SUP], Shiliang Zhang[SUP] 15 [/SUP], Menghang Xia[SUP] 13 [/SUP], Wei Zheng[SUP] 13 [/SUP], Jordi Bonaventura[SUP] 16 [/SUP], Martin G Pomper[SUP] 17 [/SUP], Jody E Hooper[SUP] 18 [/SUP], Marisela Morales[SUP] 15 [/SUP], Avi Z Rosenberg[SUP] 14 [/SUP], Kendall W Nettles[SUP] 6 [/SUP], Sanjay K Jain[SUP] 3 4 5 [/SUP], Marcello Allegretti[SUP] 19 [/SUP], Michael Michaelides[SUP] 1 20 [/SUP]
Affiliations
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.
. 2022 Dec 2;8(48):eadd4150.
doi: 10.1126/sciadv.add4150. Epub 2022 Nov 30.
The SARS-CoV-2 spike protein binds and modulates estrogen receptors
Oscar Solis[SUP] 1 [/SUP], Andrea R Beccari[SUP] 2 [/SUP], Daniela Iaconis[SUP] 2 [/SUP], Carmine Talarico[SUP] 2 [/SUP], Camilo A Ruiz-Bedoya[SUP] 3 4 5 [/SUP], Jerome C Nwachukwu[SUP] 6 [/SUP], Annamaria Cimini[SUP] 7 8 [/SUP], Vanessa Castelli[SUP] 7 [/SUP], Riccardo Bertini[SUP] 9 [/SUP], Monica Montopoli[SUP] 10 11 [/SUP], Veronica Cocetta[SUP] 10 [/SUP], Stefano Borocci[SUP] 12 [/SUP], Ingrid G Prandi[SUP] 12 [/SUP], Kelly Flavahan[SUP] 3 4 5 [/SUP], Melissa Bahr[SUP] 3 4 5 [/SUP], Anna Napiorkowski[SUP] 3 4 5 [/SUP], Giovanni Chillemi[SUP] 12 [/SUP], Masato Ooka[SUP] 13 [/SUP], Xiaoping Yang[SUP] 14 [/SUP], Shiliang Zhang[SUP] 15 [/SUP], Menghang Xia[SUP] 13 [/SUP], Wei Zheng[SUP] 13 [/SUP], Jordi Bonaventura[SUP] 16 [/SUP], Martin G Pomper[SUP] 17 [/SUP], Jody E Hooper[SUP] 18 [/SUP], Marisela Morales[SUP] 15 [/SUP], Avi Z Rosenberg[SUP] 14 [/SUP], Kendall W Nettles[SUP] 6 [/SUP], Sanjay K Jain[SUP] 3 4 5 [/SUP], Marcello Allegretti[SUP] 19 [/SUP], Michael Michaelides[SUP] 1 20 [/SUP]
Affiliations
- PMID: 36449624
- DOI: 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.