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Mol Syst Biol ; 16(7): e9610, 2020 07.
Article in English | MEDLINE | ID: covidwho-680519


The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across > 150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye, and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitute an important resource for further studies on SARS-CoV-2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.

Peptidyl-Dipeptidase A/metabolism , Respiratory System/metabolism , Betacoronavirus , Blood Vessels/metabolism , Conjunctiva/metabolism , Enterocytes/metabolism , Female , Gallbladder/metabolism , Host Microbial Interactions , Humans , Immunohistochemistry , Kidney Tubules, Proximal/metabolism , Male , Mass Spectrometry , Myocytes, Cardiac/metabolism , Organ Specificity , Peptidyl-Dipeptidase A/genetics , Placenta/metabolism , Pregnancy , RNA-Seq , Single-Cell Analysis , Testis/metabolism
Int J Mol Sci ; 21(11)2020 May 27.
Article in English | MEDLINE | ID: covidwho-382033


At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.

Anti-Inflammatory Agents/therapeutic use , Coronavirus Infections/drug therapy , Fenretinide/therapeutic use , Pneumonia, Viral/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Betacoronavirus/isolation & purification , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines , Fenretinide/pharmacology , Humans , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Respiratory System/drug effects , Respiratory System/metabolism , Signal Transduction/drug effects
Am J Physiol Lung Cell Mol Physiol ; 318(6): L1280-L1281, 2020 06 01.
Article in English | MEDLINE | ID: covidwho-326936


There is marked sexual dimorphism in the current coronavirus disease 2019 (COVID-19) pandemic. Here we report that estrogen can regulate the expression of angiotensin-converting enzyme 2 (ACE2), a key component for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry, in differentiated airway epithelial cells. Further studies are required to elucidate the mechanisms by which sex steroids regulate SARS-CoV-2 infectivity.

Betacoronavirus/drug effects , Coronavirus Infections , Estrogens/pharmacology , Pandemics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Epithelial Cells/drug effects , Epithelial Cells/virology , Estrogens/metabolism , Humans , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Respiratory System/drug effects , Respiratory System/metabolism