The Transmembrane Protease TMPRSS2 as a Therapeutic Target for COVID-19 Treatment

TMPRSS2 is a type II transmembrane protease with broad expression in epithelial cells of the respiratory and gastrointestinal tract, the prostate, and other organs. Although the physiological role of TMPRSS2 remains largely elusive, several endogenous substrates have been identified. TMPRSS2 serves as a major cofactor in SARS-CoV-2 entry, and primes glycoproteins of other respiratory viruses as well. Consequently, inhibiting TMPRSS2 activity is a promising strategy to block viral infection. In this review, we provide an overview of the role of TMPRSS2 in the entry processes of different respiratory viruses. We then review the different classes of TMPRSS2 inhibitors and their clinical development, with a focus on COVID-19 treatment.

Automated summary

TMPRSS2 is a crucial protease with widespread expression in various organs, playing a role in the entry processes of different respiratory viruses. Inhibiting TMPRSS2 activity is a promising strategy for blocking viral infections.