Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in hundreds of thousands of deaths worldwide. While the majority of people with COVID-19 won’t require hospitalization, those who do may experience severe life-threatening complications, including acute respiratory distress syndrome. SARS-CoV-2 infects human cells by binding to the cellular surface protein angiotensin-converting enzyme 2 (ACE2); in addition, the cellular transmembrane serine protease 2 (TMPRSS2) is needed for priming of the spike (S) protein of the virus. Virus entry may also depend on the activity of the endosomal/lysosomal cysteine proteases cathepsin B, L (CTSB, CTSL) although their activity is likely dispensable. Given that the uncertainty of how COVID-19 kills, hampers doctors’ ability to choose treatments the need for a deep understanding of COVID-19 biology is urgent. Herein, we performed an expression profiling meta-analysis of ACE2 , TMPRSS2 and CTSB/L genes (and proteins) in public repository databases and found that all are widely expressed in human tissues; also, the ACE2 and TMPRSS2 genes tend to be co-regulated. The ACE2 and TMPRSS genes expression is (among others) suppressed by TNF, and is induced by pro-inflammatory conditions including obesity, Barrett’s esophagus, stomach infection by helicobacter pylori , diabetes, autoimmune diseases and oxidized LDL; by exercise, as well as by growth factors, viruses’ infections, cigarette smoke, interferons and androgens. Regarding currently investigated therapies interferon-beta induced ACE2 gene expression in bronchial epithelial cells, while chloroquine tends to upregulate CTSB/L genes. Finally, we analyzed KEGG pathways modulated by ACE2, TMPRSS2 and CTSB/L and probed DrugBank for drugs that target modules of the affected pathways. Our data indicate possible novel high-risk groups for COVID-19; provide a rich resource for future investigations of its pathogenesis and highlight the therapeutic challenges we face. Graphical abstract Image 1 Highlights • ACE2 and TMPRSS2 genes tend to be co-regulated and are suppressed by TNF. • Pro-inflammatory conditions, interferons and androgens induce ACE2 , TMPRSS2 genes. • Cathepsins CTSB/L are widely expressed in human tissues. • Various druggable pathways can be targeted to mitigate SARS-CoV-2 infectivity.
【저자키워드】 COVID-19, SARS-CoV-2, ACE2, TMPRSS2, Gene Expression, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, ACE2, angiotensin-converting enzyme 2, TMPRSS2, transmembrane protease, serine 2, ACE, angiotensin-converting enzyme, GEO, Gene Expression Omnibus, CTSB/L, CTSB/L, cathepsins B/L,