Found at: origin.rxivist.org:70/papers/190020

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                      TRENDING OPEN SCIENCE
The SARS-CoV-2 spike protein binds and modulates estrogen receptors
  Oscar Solis
  Andrea R. Beccari
  Daniela Iaconis
  Carmine Talarico
  Camilo A. Ruiz-Bedoya
  Jerome C. Nwachukwu
  Annamaria Cimini
  Vanessa Castelli
  Riccardo Bertini
  Monica Montopoli
  Veronica Cocetta
  Stefano Borocci
  Ingrid G. Prandi
  Kelly Flavahan
  Melissa Bahr
  Anna Napiorkowski
  Giovanni Chillemi
  Masato Ooka
  Xiaoping Yang
  Shiliang Zhang
  Menghang Xia
  Wei Zheng
  Jordi Bonaventura
  Martin G. Pomper
  Jody E. Hooper
  Marisela Morales
  Avi Z Rosenberg
  Kendall W Nettles
  Sanjay K Jain
  Marcello Allegretti
  Michael Michaelides
DOI: 10.1101/2022.05.21.492920
On bioRxiv: https://biorxiv.org/content/10.1101/2022.05.21.492920v1
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike
(S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell
nfection. 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
n 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-ER binding mode. In cultured cells, S DNA transfection
ncreased ER cytoplasmic accumulation, and S treatment induced ER-
multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using
[18F]fluoroestradiol (FES) localized lung pathology with increased ER
lung levels. Postmortem experiments in lung tissues from SARS-
CoV-2-infected hamsters and humans confirmed an increase in
cytoplasmic ER expression and its colocalization with S protein in
alveolar macrophages. These findings describe the discovery and
characterization of a novel S-ER interaction, imply a role for S as an
NRC, and are poised to advance knowledge of SARS-CoV-2 biology,
COVID-19 pathology, and mechanisms of sex differences in the pathology
of infectious disease.
  - Overall rank: 35479
  - Rank in immunology: 1329
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