美国加州大学旧金山分校Faranak Fattahi、Hani Goodarzi等研究人员合作发现，雄激素信号调节SARS-CoV-2受体水平，并与男性的严重COVID-19症状相关。相关论文于2020年11月17日在线发表在《细胞—干细胞》杂志上。
Title: Androgen Signaling Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men
Author: 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, Michel Tassetto, Sara Sunshine, Sina Farahvashi, Ali Kalantari, Wei Liu, Raul Andino, Hongyu Zhao, Pradeep Natarajan, David J. Erle, Melanie Ott, Hani Goodarzi, Faranak Fattahi
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 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.
Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：21.464