The SARS-CoV-2 spike protein binds and modulates estrogen receptors.


Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
23 May 2022
Historique:
entrez: 6 6 2022
pubmed: 7 6 2022
medline: 7 6 2022
Statut: epublish

Résumé

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ERα). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ERα binding mode. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using [

Identifiants

pubmed: 35665018
doi: 10.1101/2022.05.21.492920
pmc: PMC9164441
pii:
doi:

Types de publication

Preprint

Langues

eng

Commentaires et corrections

Type : UpdateIn

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Auteurs

Oscar Solis (O)

Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, 21224, MD, USA.

Andrea R Beccari (AR)

EXSCALATE, Dompé farmaceutici S.p.A, Napoli, Italy.

Daniela Iaconis (D)

EXSCALATE, Dompé farmaceutici S.p.A, Napoli, Italy.

Carmine Talarico (C)

EXSCALATE, Dompé farmaceutici S.p.A, Napoli, Italy.

Camilo A Ruiz-Bedoya (CA)

Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Jerome C Nwachukwu (JC)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.

Annamaria Cimini (A)

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.
Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, Temple University, Philadelphia, PA, USA.

Vanessa Castelli (V)

Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

Riccardo Bertini (R)

Atreius S.a.s., L'Aquila, Italy.

Monica Montopoli (M)

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
VIMM- Veneto Institute of Molecular Medicine, Fondazione per la Ricerca Biomedica Avanzata, Padova, Italy.

Veronica Cocetta (V)

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.

Stefano Borocci (S)

Department for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Viterbo, Italy.

Ingrid G Prandi (IG)

Department for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Viterbo, Italy.

Kelly Flavahan (K)

Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Melissa Bahr (M)

Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Anna Napiorkowski (A)

Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Giovanni Chillemi (G)

Department for Innovation in Biological, Agro-Food and Forest Systems, DIBAF, University of Tuscia, Viterbo, Italy.

Masato Ooka (M)

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Rockville, MD, USA.

Xiaoping Yang (X)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Shiliang Zhang (S)

Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, 21224, MD, USA.

Menghang Xia (M)

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Rockville, MD, USA.

Wei Zheng (W)

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Rockville, MD, USA.

Jordi Bonaventura (J)

Departament de Patologia i Terapèutica Experimental, Institut de Neurociències, Universitat de Barcelona, L'Hospitalet de Llobregat, Catalonia.

Martin G Pomper (MG)

Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Jody E Hooper (JE)

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.

Marisela Morales (M)

Neuronal Networks Section, National Institute on Drug Abuse Intramural Research Program, Baltimore, 21224, MD, USA.

Avi Z Rosenberg (AZ)

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Kendall W Nettles (KW)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.

Sanjay K Jain (SK)

Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pediatrics, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB-II Room 109, Baltimore, MD, USA.
Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Marcello Allegretti (M)

Dompé farmaceutici S.p.A, L'Aquila, Italy.

Michael Michaelides (M)

Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, 21224, MD, USA.
Department of Psychiatry & Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Classifications MeSH