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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; 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.
Afiliación
  • Solis O; Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
  • Beccari AR; EXSCALATE, Dompé farmaceutici S.p.A, Napoli, Italy.
  • Iaconis D; EXSCALATE, Dompé farmaceutici S.p.A, Napoli, Italy.
  • Talarico C; EXSCALATE, Dompé farmaceutici S.p.A, Napoli, Italy.
  • Ruiz-Bedoya CA; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Nwachukwu JC; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD 21287, USA.
  • Cimini A; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Castelli V; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
  • Bertini R; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
  • Montopoli M; Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, Temple University, Philadelphia, PA 19122, USA.
  • Cocetta V; Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
  • Borocci S; Atreius S.a.s., L'Aquila, Italy.
  • Prandi IG; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
  • Flavahan K; VIMM- Veneto Institute of Molecular Medicine, Fondazione per la Ricerca Biomedica Avanzata, Padova, Italy.
  • Bahr M; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
  • Napiorkowski A; Department for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Viterbo, Italy.
  • Chillemi G; Department for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Viterbo, Italy.
  • Ooka M; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Yang X; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD 21287, USA.
  • Zhang S; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Xia M; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Zheng W; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD 21287, USA.
  • Bonaventura J; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Pomper MG; Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Hooper JE; Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD 21287, USA.
  • Morales M; Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Rosenberg AZ; Department for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Viterbo, Italy.
  • Nettles KW; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Rockville, MD 20850, USA.
  • Jain SK; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Allegretti M; Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD 21224, USA.
  • Michaelides M; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Rockville, MD 20850, USA.
Sci Adv ; 8(48): eadd4150, 2022 12 02.
Article en En | MEDLINE | ID: mdl-36449624
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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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Glicoproteína de la Espiga del Coronavirus / COVID-19 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Glicoproteína de la Espiga del Coronavirus / COVID-19 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos