Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzaltamide

An anti-androgen drug, enzalutamide, was proposed to be an effective antiviral against SARS-CoV-2 because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), which is a key component that mediates the cell entry of SARS-CoV-2. Although enzalutamide efficiently inhibited viral infection in prostate cancer cells, it did not exhibit an antiviral effect in the lung organoid as well as the lung of mice pre-infected with hACE2 expressing adenovirus vector. The lung cells express TMPRSS2 with androgen-independent manner. These results indicate that the enzaltamide is not efective for respiratory infection of SARS-CoV-2.