TY - JOUR
T1 - Targeting TMPRSS2 in SARS-CoV-2 Infection
AU - Baughn, Linda B.
AU - Sharma, Neeraj
AU - Elhaik, Eran
AU - Sekulic, Aleksandar
AU - Bryce, Alan H.
AU - Fonseca, Rafael
N1 - Funding Information:
The genotype-tissue expression (GTEx) project was supported by the Common Fund of the Office of the Director of the National Institutes of Health , and by NCI , NHGRI , NHLBI , NIDA , NIMH , and NINDS . The data used for the analyses described in this manuscript were obtained from the GTEx Analysis Release V8 (dbGaP Accession phs000424.v8.p2) from The Human Protein Atlas GTEx data (RNAseq based on RSEMv1.2.22 [v7]) on April 15, 2020.
Funding Information:
The genotype-tissue expression (GTEx) project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Analysis Release V8 (dbGaP Accession phs000424.v8.p2) from The Human Protein Atlas GTEx data (RNAseq based on RSEMv1.2.22 [v7]) on April 15, 2020.
Publisher Copyright:
© 2020
PY - 2020/9
Y1 - 2020/9
N2 - Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has rapidly caused a global pandemic associated with a novel respiratory infection: coronavirus disease-19 (COVID-19). Angiotensin-converting enzyme-2 (ACE2) is necessary to facilitate SARS-CoV-2 infection, but—owing to its essential metabolic roles—it may be difficult to target it in therapies. Transmembrane protease serine 2 (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 displays the highest expression of TMPRSS2. Given the increased severity of disease among older men with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in severity of disease. We show that expression levels of ACE2 and TMPRSS2 are overall comparable between men and women 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 severity of SARS CoV-2. 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.
AB - Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has rapidly caused a global pandemic associated with a novel respiratory infection: coronavirus disease-19 (COVID-19). Angiotensin-converting enzyme-2 (ACE2) is necessary to facilitate SARS-CoV-2 infection, but—owing to its essential metabolic roles—it may be difficult to target it in therapies. Transmembrane protease serine 2 (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 displays the highest expression of TMPRSS2. Given the increased severity of disease among older men with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in severity of disease. We show that expression levels of ACE2 and TMPRSS2 are overall comparable between men and women 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 severity of SARS CoV-2. 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.
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U2 - 10.1016/j.mayocp.2020.06.018
DO - 10.1016/j.mayocp.2020.06.018
M3 - Article
C2 - 32861340
AN - SCOPUS:85089811154
VL - 95
SP - 1989
EP - 1999
JO - Mayo Clinic Proceedings
JF - Mayo Clinic Proceedings
SN - 0025-6196
IS - 9
ER -