TMPRSS2, Required for SARS-CoV-2 Entry, Is Downregulated in Lung Cells by Enzalutamide, a Prostate Cancer Therapeutic

Three years ago, a study found that the SARS-CoV-2 coronavirus, responsible for the COVID-19 pandemic, requires two host cell surface proteins, ACE2 and TMPRSS2, to enter lung cells. The research showed that TMPRSS2, a target of the androgen receptor, could be reduced in human lung cells by treatment with the antiandrogen enzalutamide, a drug commonly used in advanced prostate cancer. This treatment also significantly decreased Tmprss2 levels in the lungs of mice. Analysis of existing datasets revealed a notable co-expression of AR and TMPRSS2 in specific lung cell types targeted by SARS-CoV-2. These findings strongly suggested the potential of antiandrogens as a treatment option for COVID-19, warranting further clinical trials.