COVID-19 and Liquid Homeostasis in the Lung-A Perspective through the Epithelial Sodium Channel (ENaC) Lens

Cells. 2022 May 31;11(11):1801. doi: 10.3390/cells11111801.

Abstract

Infections with a new corona virus in 2019 lead to the definition of a new disease known as Corona Virus Disease 2019 (COVID-19). The sever cases of COVID-19 and the main cause of death due to virus infection are attributed to respiratory distress. This is associated with the formation of pulmonary oedema that impairs blood oxygenation and hypoxemia as main symptoms of respiratory distress. An important player for the maintenance of a defined liquid environment in lungs needed for normal lung function is the epithelial sodium channel (ENaC). The present article reviews the implications of SARS-CoV-2 infections from the perspective of impaired function of ENaC. The rationale for this perspective is derived from the recognition that viral spike protein and ENaC share a common proteolytic cleavage site. This cleavage site is utilized by the protease furin, that is essential for ENaC activity. Furin cleavage of spike 'activates' the virus protein to enable binding to host cell membrane receptors and initiate cell infection. Based on the importance of proteolytic cleavage for ENaC function and activation of spike, it seems feasible to assume that virus infections are associated with impaired ENaC activity. This is further supported by symptoms of COVID-19 that are reminiscent of impaired ENaC function in the respiratory tract.

Keywords: COVID-19; SARS-CoV-2; airway liquid; alveolar liquid; epithelial Na+ channel; proteases; proteolytic cleavage; transepithelial ion transport.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Epithelial Sodium Channels / metabolism
  • Furin / metabolism
  • Homeostasis
  • Humans
  • Lung / metabolism
  • Peptide Hydrolases / metabolism
  • Respiratory Distress Syndrome*
  • SARS-CoV-2
  • Viral Proteins / metabolism

Substances

  • Epithelial Sodium Channels
  • Viral Proteins
  • Peptide Hydrolases
  • Furin

Grants and funding

Work on this project was enabled by funding provided from the Health Research Council of New Zealand (Explorer Grant 21/727).