Targeting TMPRSS2 in SARS-CoV-2 infection

Baughn, Linda B.; Sharma, Neeraj; Elhaik, Eran; Sekulic, Aleksandar; Bryce, Alan H.; Fonseca, Rafael

Abstract SARS-coronavirus 2 (SARS-CoV-2) has rapidly caused a global pandemic associated with a novel respiratory infection now termed coronavirus disease-19 (COVID-19). ACE2 is necessary to facilitate SARS-CoV-2 infection, but due to its essential metabolic roles, it may be difficult to target it in therapies. TMPRSS2, which interacts with ACE2, may be a better candidate for targeted therapies. Using publicly-available expression data, we show that both ACE2 and TMPRSS2 are expressed in many host tissues, including lung. The highest expression of ACE2 is found in the testes, whereas the prostate display the highest expression of TMPRSS2. Given the increased severity of disease among older males with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in disease severity. We show that expression levels of ACE2 and TMPRSS2 are overall comparable between males and females in multiple tissues suggesting that differences in the expression levels of TMPRSS2 and ACE2 in the lung and other non-sex-specific tissues may not explain the gender disparities in SARS CoV-2 severity. However, given their instrumental roles for SARS-CoV-2 infection and their pleiotropic expression, targeting the activity and expression levels of TMPRSS2 is a rational approach to treat COVID-19.