SARS-CoV-2 receptor ACE2 is co-expressed with genes related to transmembrane serine proteases, viral entry, immunity and cellular stress

Sci Rep. 2020 Dec 8;10(1):21415. doi: 10.1038/s41598-020-78402-2.


The COVID-19 pandemic resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December 2019 in Wuhan in China has placed immense burden on national economies and global health. At present neither vaccination nor therapies are available. Here, we performed a meta-analysis of RNA-sequencing data from three studies employing human lung epithelial cells. Of these one focused on lung epithelial cells infected with SARS-CoV-2. We aimed at identifying genes co-expressed with angiotensin I converting enzyme 2 (ACE2) the human cell entry receptor of SARS-CoV-2, and unveiled several genes correlated or inversely correlated with high significance, among the most significant of these was the transmembrane serine protease 4 (TMPRSS4). Serine proteases are known to be involved in the infection process by priming the virus spike protein. Pathway analysis revealed virus infection amongst the most significantly correlated pathways. Gene Ontologies revealed regulation of viral life cycle, immune responses, pro-inflammatory responses- several interleukins such as IL6, IL1, IL20 and IL33, IFI16 regulating the interferon response to a virus, chemo-attraction of macrophages, and cellular stress resulting from activated Reactive Oxygen Species. We believe that this dataset will aid in a better understanding of the molecular mechanism(s) underlying COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • COVID-19 / pathology
  • Computational Biology
  • Epithelial Cells / metabolism*
  • Humans
  • Interleukin-1beta / immunology
  • Interleukin-33 / immunology
  • Interleukin-6 / immunology
  • Interleukins / immunology
  • Lung / cytology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nuclear Proteins / immunology
  • Phosphoproteins / immunology
  • Reactive Oxygen Species / metabolism
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism*
  • SARS-CoV-2 / metabolism*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Transcriptome / genetics


  • IL1B protein, human
  • IL33 protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-33
  • Interleukin-6
  • Interleukins
  • Membrane Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Reactive Oxygen Species
  • Receptors, Virus
  • IFI16 protein, human
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS4 protein, human
  • interleukin 20