Abstract
BackgroundSevere acute respiratory syndrome (SARS)-CoV-2-induced coronavirus disease-2019 (COVID-19) is a pandemic disease that affects > 2.8 million people worldwide, with numbers increasing dramatically daily. However, there is no specific treatment for COVID-19 and much remains unknown about this disease. Angiotensin-converting enzyme (ACE)2 is a cellular receptor of SARS-CoV-2. It is cleaved by type II transmembrane serine protease (TMPRSS)2 and disintegrin and metallopeptidase domain (ADAM)17 to assist viral entry into host cells. Clinically, SARS-CoV-2 infection may result in acute lung injury and lung fibrosis, but the underlying mechanisms of COVID-19 induced lung fibrosis are not fully understood.MethodsThe networks of ACE2 and its interacting molecules were identified using bioinformatic methods. Their gene and protein expressions were measured in human epithelial cells after 24 h SARS-CoV-2 infection, or in existing datasets of lung fibrosis patients.ResultsWe confirmed the binding of SARS-CoV-2 and ACE2 by bioinformatic analysis. TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells. SARS-CoV-2 infection increased ACE2, TGFB1, CTGF and FN1 mRNA that were drivers of lung fibrosis. These changes were also found in lung tissues from lung fibrosis patients.ConclusionsTherefore, SARS-CoV-2 binds with ACE2 and activates fibrosis-related genes and processes to induce lung fibrosis.
Highlights
Severe acute respiratory syndrome (SARS)-CoV-2-induced coronavirus disease-2019 (COVID-19) is a pandemic disease that affects > 2.8 million people worldwide, with numbers increasing dramatically daily
Network of Angiotensin-converting enzyme 2 (ACE2) and selected interacting factors in SARA S-CoV-2 infection We confirmed that the main S protein of SARS-CoV bound to ACE2 protein using p-hipster analysis (Fig. 1a), which is consistent with previous studies
To understand the process of SARS-CoV-2 binding, we identified the network of ACE2 and its interacting genes using Gene MANIA [18]
Summary
Severe acute respiratory syndrome (SARS)-CoV-2-induced coronavirus disease-2019 (COVID-19) is a pandemic disease that affects > 2.8 million people worldwide, with numbers increasing dramatically daily. Angiotensin-converting enzyme (ACE) is a cellular receptor of SARS-CoV-2. It is cleaved by type II transmembrane serine protease (TMPR SS) and disintegrin and metallopeptidase domain (ADAM) to assist viral entry into host cells. CoV infection results in lethal respiratory diseases, including severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and coronavirus disease-2019 (COVID-19). SARS induced by SARS-related coronavirus (SARS-CoV) affected 8096 patients from 2002 to 2003 with a fatality rate of 9.6% worldwide [1]. MERS-related coronavirus (MERS-CoV) affected 2519 cases with a high fatality of 34.4% [2]. The lack of deep understanding of SARSCoV-2 is hampering vaccine development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
