Androgen Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men.

BioRxiv : the Preprint Server for Biology
Zaniar GhazizadehFaranak Fattahi

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a global health crisis, and yet our understanding of the disease pathophysiology and potential treatment options remains limited. SARS-CoV-2 infection occurs through binding and internalization of the viral spike protein to angiotensin converting enzyme 2 (ACE2) on the host cell membrane. Lethal complications are caused by damage and failure of vital organs that express high levels of ACE2, including the lungs, the heart and the kidneys. Here, we established a high-throughput drug screening strategy to identify therapeutic candidates that reduce ACE2 levels in human embryonic stem cell (hESC) derived cardiac cells. Drug target analysis of validated hit compounds, including 5 alpha reductase inhibitors, revealed androgen signaling as a key modulator of ACE2 levels. Treatment with the 5 alpha reductase inhibitor dutasteride reduced ACE2 levels and internalization of recombinant spike receptor binding domain (Spike-RBD) in hESC-derived cardiac cells and human alveolar epithelial cells. Finally, clinical data on coronavirus disease 2019 (COVID-19) patients demonstrated that abnormal androgen states are significantly associated with severe disease comp...Continue Reading

Citations

Oct 1, 2020·BMC Endocrine Disorders·Flavio A Cadegiani
Jan 14, 2021·Journal of Biomedical Science·Ioannis P TrougakosMeletios A Dimopoulos
Nov 13, 2020·Endocrine·Mohamed S MohamedHelgi B Schiöth
Jan 1, 2021·Cell & Bioscience·Miriam Marlene Medina-EnríquezTalia Wegman-Ostrosky
Oct 29, 2020·Nature Communications·Qingpin XiaoCheng Zhang
Feb 16, 2021·AIDS Research and Human Retroviruses·Monty Montano
May 7, 2021·Journal of Environmental and Public Health·Zemene Demelash KifleEngidaw Fentahun Enyew
Aug 17, 2021·Frontiers in Immunology·Xiaolu LiTao Yu
Oct 17, 2020·ACS Pharmacology & Translational Science·Qiongqiong Angela ZhouSteven Watkins

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Datasets Mentioned

BETA
SRR7120642

Methods Mentioned

BETA
ChIP-seq
biopsy
FACS
RNA-seq
PCR

Software Mentioned

bestNormalize
ConvMolFeaturizer
SEA
vHTS
RData
R
scikit
SNOMED
Salmon
SeuratWrappers

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