Our findings validated that enzalutamide significantly inhibits SARS-CoV-2 infection in AR and TMPRSS2 double positive prostate cancer cells, identified that enzalutamide does not exhibit antiviral activity in human lung cancer cells and patients-derived benign lung organoids in vitro and in the lungs of Ad-ACE2-transduced WT mice in vivo, and demonstrated the distinct AR binding pattern between prostate and lung epithelial cells. Here, AR is linked to lung carcinoma.