Targeting transcriptional regulation of SARS-CoV-2 entry factors <i>ACE2</i> and <i>TMPRSS2</i>
Yuanyuan Qiao, Xiaoming Wang, Rahul Mannan, Sethuramasundaram Pitchiaya, Yuping Zhang, Jesse W. Wotring, Lanbo Xiao, Dan R. Robinson, Yi‐Mi Wu, Jean C. Tien, Xuhong Cao, Stephanie A. Simko, Ingrid J. Apel, Pushpinder Bawa, Steven Kregel, Sathiya Pandi Narayanan, Gregory Raskind, Stephanie J. Ellison, Abhijit Parolia, Sylvia Zelenka-Wang, Lisa McMurry, Fengyun Su, Rui Wang, Yunhui Cheng, Andrew Delekta, Zejie Mei, Carla D. Pretto, Shaomeng Wang, Rohit Mehra, Jonathan Z. Sexton, Arul M. Chinnaiyan
Abstract
Significance New therapeutic targets are urgently needed against SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Results in this study show that targeting the transcriptional regulation of host entry factors TMPRSS2 and ACE2 is a viable treatment strategy to prevent SARS-CoV-2 infection. In particular, inhibitors of androgen receptor (AR) or bromodomain and extraterminal domain (BET) proteins are effective against SARS-CoV-2 infection. AR inhibitors are already approved in the clinic for treatment of prostate cancer and are under investigation in COVID-19 patients; BET inhibitors are also in clinical development for other indications and could be rapidly repurposed for COVID-19.