Coronavirus disease 2019 (COVID-19) emerged at the end of 2019 and spread rapidly, resulting in a global pandemic. In the development of therapies for COVID-19, it was found that SARS-CoV-2 encodes non-structural and structural proteins necessary for its viral life cycle. Among these, the spike glycoprotein plays a crucial role in SARS-CoV-2 infection by recognizing and attaching to the transmembrane ACE2 protein on host cells. This protein is also cleaved and activated by the cell surface enzyme TMPRSS2 to facilitate membrane fusion and entry. In mouse models, inhibiting TMPRSS2 function can reduce SARS-CoV-2 entry into lung cells, with similar observations shown when ACE2 function is inhibited. Additionally, it became apparent that there are gender differences in the severity of COVID-19, with males having higher hospitalization and mortality rates than females. Data have shown that treatment with antiandrogens reduces TMPRSS2 in human lung cells and dramatically lowers TMPRSS2 levels in mouse lungs. The study assessed live SARS-CoV-2 infection in human lung cells and observed a significant reduction in viral entry and infection after treatment with antiandrogens. Along with the co-expression of AR and TMPRSS2 in specific lung cell types targeted by SARS-CoV-2, this data provides strong evidence to support clinical trials evaluating the efficacy of antiandrogens as a treatment option for COVID-19.