In the early stages of the COVID-19 pandemic, Transmembrane Protease, Serine-2 (TMPRSS2) was identified as an important host protease enabling viral entry of SARS-CoV-2 . TMPRSS2 is responsible for cleaving the SARS-CoV-2 Spike (S) protein after it has docked to its primary receptor, angiotensin converting enzyme (ACE2; Fig. ) . TMPRSS2 S protein cleavage drives conformational changes in the S protein that induce membrane fusion between the virus and host . TMPRSS2 has also been implicated in the entry of other human respiratory viruses including MERS-CoV, SARS-CoV, and HKU1 as well other viruses including para-influenza virus and Sendai virus through similar entry mechanisms . This widespread role of TMPRSS2 as a respiratory virus entry factor makes TMPRSS2 an interesting target for the development of a broadly active antiviral agent against a diverse range of respiratory viruses .