The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells

Abstract SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 TMPRSS2. Downregulation of one or both these is thus a potential therapeutic approach for COVID-19. TMPRSS2 known target androgen receptor, ligand-activated transcription factor; receptor activation increases levels in tissues, notably prostate. We show here that treatment with antiandrogen enzalutamide—a well-tolerated drug widely used advanced prostate cancer—reduces human lung cells mouse lung. Importantly, antiandrogens significantly reduced infection cells. In support this experimental data, analysis existing datasets shows striking co-expression AR TMPRSS2, including specific types targeted by SARS-CoV-2. Together, data presented provides strong evidence to clinical trials assess efficacy as option