Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men.
Cell Stem Cell
; 27(6): 876-889.e12, 2020 12 03.
Article
in English
| MEDLINE | ID: covidwho-927293
ABSTRACT
SARS-CoV-2 infection has led to a global health crisis, and yet our understanding of the disease and potential treatment options remains limited. The infection occurs through binding of the virus with angiotensin converting enzyme 2 (ACE2) on the cell membrane. Here, we established a screening strategy to identify drugs that reduce ACE2 levels in human embryonic stem cell (hESC)-derived cardiac cells and lung organoids. Target analysis of hit compounds revealed androgen signaling as a key modulator of ACE2 levels. Treatment with antiandrogenic drugs reduced ACE2 expression and protected hESC-derived lung organoids against SARS-CoV-2 infection. Finally, clinical data on COVID-19 patients demonstrated that prostate diseases, which are linked to elevated androgen, are significant risk factors and that genetic variants that increase androgen levels are associated with higher disease severity. These findings offer insights on the mechanism of disproportionate disease susceptibility in men and identify antiandrogenic drugs as candidate therapeutics for COVID-19.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Signal Transduction
/
Patient Acuity
/
Receptors, Coronavirus
/
Angiotensin-Converting Enzyme 2
/
COVID-19
/
Androgens
Type of study:
Prognostic study
Topics:
Long Covid
/
Traditional medicine
/
Variants
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Cell Stem Cell
Year:
2020
Document Type:
Article
Affiliation country:
J.stem.2020.11.009
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