@article{3025755,
    title = "Expression profiling meta-analysis of ACE2 and TMPRSS2, the putative anti-inflammatory receptor and priming protease of SARS-CoV-2 in human cells, and identification of putative modulators",
    author = "Gkogkou, E. and Barnasas, G. and Vougas, K. and Trougakos, I.P.",
    journal = "Redox Biology",
    year = "2020",
    volume = "36",
    publisher = "Elsevier B.V.",
    issn = "2213-2317",
    doi = "10.1016/j.redox.2020.101615",
    keywords = "angiotensin converting enzyme 2;  cathepsin B;  serine proteinase;  transmembrane serine protease 2;  unclassified drug;  viral protein;  angiotensin converting enzyme 2;  cathepsin;  dipeptidyl carboxypeptidase;  dipeptidyl carboxypeptidase inhibitor;  serine proteinase;  serine proteinase inhibitor;  TMPRSS2 protein, human, ACE2 gene;  Article;  autoimmune disease;  Barrett esophagus;  controlled study;  coronavirus disease 2019;  diabetes mellitus;  epithelium cell;  gene;  gene expression;  gene expression profiling;  genetic database;  Helicobacter infection;  human;  human cell;  obesity;  pathogenesis;  priority journal;  protein binding;  SARS coronavirus;  smoking;  TMPRSS2 gene;  virus entry;  Betacoronavirus;  drug effect;  gene expression profiling;  genetics;  intestine mucosa;  kidney;  meta analysis;  metabolism;  physiology;  respiratory mucosa, Angiotensin-Converting Enzyme Inhibitors;  Betacoronavirus;  Cathepsins;  Gene Expression Profiling;  Humans;  Intestinal Mucosa;  Kidney;  Peptidyl-Dipeptidase A;  Respiratory Mucosa;  Serine Endopeptidases;  Serine Proteinase Inhibitors;  Virus Internalization",
    abstract = "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. © 2020 The Author(s)"
}