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

Ryan M. Samuel, Homa Majd, Mikayla N. Richter, Zaniar Ghazizadeh, Seyedeh Maryam Zekavat, Albertas Navickas, Jonathan T. Ramirez, Hosseinali Asgharian, Camille R. Simoneau, Luke R. Bonser, Kyung Duk Koh, Miguel Garcia-Knight (+12 others)
2020 Cell Stem Cell  
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
more » ... tor 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.
doi:10.1016/j.stem.2020.11.009 pmid:33232663 pmcid:PMC7670929 fatcat:d7rxvl24g5cgrfdokj5wtbq2lq