{"doi":"10.1126/sciadv.add4150","title":"The SARS-CoV-2 spike protein binds and modulates estrogen receptors","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.","journal":"Science Advances","year":2022,"id":239621,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9633,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":865754,"name":"Andrea R. Beccari","orcid":"0000-0001-6830-2695","position":1,"is_corresponding":false},{"id":865755,"name":"Daniela Iaconis","orcid":"0000-0002-1052-6634","position":2,"is_corresponding":false},{"id":865756,"name":"Carmine Talarico","orcid":"0000-0003-4789-0955","position":3,"is_corresponding":false},{"id":241542,"name":"Camilo A. Ruiz-Bedoya","orcid":"0000-0002-0653-4244","position":4,"is_corresponding":false},{"id":824065,"name":"J.C. Nwachukwu","orcid":"0000-0003-4313-9187","position":5,"is_corresponding":false},{"id":865757,"name":"Annamaria Cimini","orcid":"0000-0002-2737-7970","position":6,"is_corresponding":false},{"id":415626,"name":"Vanessa Castelli","orcid":"0000-0002-7005-3218","position":7,"is_corresponding":false},{"id":866622,"name":"Riccardo Bertini","orcid":null,"position":8,"is_corresponding":false},{"id":860425,"name":"Monica Montopoli","orcid":"0000-0001-6182-4132","position":9,"is_corresponding":false},{"id":860414,"name":"Veronica Cocetta","orcid":"0000-0002-0350-8403","position":10,"is_corresponding":false},{"id":865758,"name":"Stefano Borocci","orcid":"0000-0003-4931-3019","position":11,"is_corresponding":false},{"id":865759,"name":"Ingrid G. Prandi","orcid":"0000-0002-3253-1821","position":12,"is_corresponding":false},{"id":637581,"name":"Kelly Flavahan","orcid":null,"position":13,"is_corresponding":false},{"id":636792,"name":"Melissa Bahr","orcid":"0000-0002-0278-000X","position":14,"is_corresponding":false},{"id":865760,"name":"Anna Napiorkowski","orcid":"0000-0002-8937-0926","position":15,"is_corresponding":false},{"id":244671,"name":"Giovanni Chillemi","orcid":"0000-0003-3901-6926","position":16,"is_corresponding":false},{"id":355261,"name":"Masato Ooka","orcid":"0000-0002-2729-2619","position":17,"is_corresponding":false},{"id":768127,"name":"Xiaoping Yang","orcid":"0000-0003-1263-2710","position":18,"is_corresponding":false},{"id":865761,"name":"Shiliang Zhang","orcid":"0000-0001-8414-6178","position":19,"is_corresponding":false},{"id":355263,"name":"Menghang Xia","orcid":"0000-0001-7285-8469","position":20,"is_corresponding":false},{"id":227992,"name":"Wei Zheng","orcid":"0000-0003-1034-0757","position":21,"is_corresponding":false},{"id":449147,"name":"Jordi Bonaventura","orcid":"0000-0002-4745-0151","position":22,"is_corresponding":false},{"id":7932,"name":"Martin G. Pomper","orcid":"0000-0001-6753-3010","position":23,"is_corresponding":false},{"id":278995,"name":"Jody E. Hooper","orcid":"0000-0002-8209-3559","position":24,"is_corresponding":false},{"id":262801,"name":"Marisela Morales","orcid":"0000-0002-3845-9402","position":25,"is_corresponding":false},{"id":235991,"name":"Avi Z. Rosenberg","orcid":"0000-0003-2356-950X","position":26,"is_corresponding":false},{"id":444202,"name":"K.W. Nettles","orcid":"0000-0003-2917-7574","position":27,"is_corresponding":false},{"id":241543,"name":"Sanjay K. Jain","orcid":"0000-0001-9620-7070","position":28,"is_corresponding":false},{"id":865762,"name":"Marcello Allegretti","orcid":"0000-0002-0617-0233","position":29,"is_corresponding":false},{"id":620553,"name":"Michael Michaelides","orcid":"0000-0003-0398-4917","position":30,"is_corresponding":false},{"id":620552,"name":"Óscar Solís","orcid":"0000-0002-8285-5891","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:22:41.699779Z","pmid":"36449624","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}