The Antiandrogen Enzalutamide Downregulates TMPRSS2 and Reduces Cellular Entry of SARS-CoV-2 in Human Lung Cells

The document reports a study on the effects of the antiandrogen drug enzalutamide (ENZA) on the protein TMPRSS2, which is known to facilitate the entry of SARS-CoV-2 into cells. The study found that ENZA can downregulate TMPRSS2 levels in human lung cells and mouse lung tissue, leading to a significant decrease in SARS-CoV-2 cellular entry and infection. In vivo experiments with mice and in vitro experiments with A549 lung cells expressing the ACE2 receptor showed that ENZA and another antiandrogen, bicalutamide (BIC), significantly reduced viral entry and infection. The study supports the hypothesis that androgen receptor activation increases TMPRSS2 levels and suggests that antiandrogens could be a potential therapeutic option for COVID-19. The findings also highlight the potential for antiandrogen therapy to be well-tolerated in both men and women, proposing clinical trials to assess the efficacy of antiandrogens in treating COVID-19.