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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.

Targeting transcriptional regulation of SARS-CoV-2 entry factorsACE2andTMPRSS2