Increasing host cellular receptor-angiotensin-converting enzyme 2 expression by coronavirus may facilitate 2019-nCoV (or SARS-CoV-2) infection

J Med Virol. 2020 Nov;92(11):2693-2701. doi: 10.1002/jmv.26139. Epub 2020 Jul 2.

Abstract

The ongoing outbreak of a new coronavirus (2019-nCoV, or severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) has caused an epidemic of the acute respiratory syndrome known as coronavirus disease (COVID-19) in humans. SARS-CoV-2 rapidly spread to multiple regions of China and multiple other countries, posing a serious threat to public health. The spike (S) proteins of SARS-CoV-1 and SARS-CoV-2 may use the same host cellular receptor, angiotensin-converting enzyme 2 (ACE2), for entering host cells. The affinity between ACE2 and the SARS-CoV-2 S protein is much higher than that of ACE2 binding to the SARS-CoV S protein, explaining why SARS-CoV-2 seems to be more readily transmitted from human to human. Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS-CoV-1 and SARS-CoV-2, or by the stimulation with inflammatory cytokines such as interferons. We propose that SARS-CoV-2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread; high inflammatory cytokine levels increase ACE2 expression and act as high-risk factors for developing COVID-19, and the infection of other viruses may increase the risk of SARS-CoV-2 infection. Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses.

Keywords: 2019-nCoV; ACE2; COVID-19; IFN; ISG; SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics*
  • Angiotensin-Converting Enzyme 2 / immunology
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Gene Expression
  • HEK293 Cells
  • Humans
  • Interferons / pharmacology
  • Microarray Analysis
  • Protein Binding
  • Receptors, Virus / genetics*
  • Receptors, Virus / immunology
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / pathogenicity*
  • Severe acute respiratory syndrome-related coronavirus / genetics
  • Severe acute respiratory syndrome-related coronavirus / pathogenicity
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / immunology
  • Up-Regulation

Substances

  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV
  • spike protein, SARS-CoV-2
  • Interferons
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2