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Infection of Primary Nasal Epithelial Cells Grown at an Air-Liquid Interface to Characterize Human Coronavirus-Host Interactions
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COVID-19 and Liquid Homeostasis in the Lung-A Perspective through the Epithelial Sodium Channel (ENaC) Lens

Emily F Brown1,2, Tamapuretu Mitaera1,2, Martin Fronius1,2,3,4

  • 1Department of Physiology, University of Otago, Dunedin 9054, New Zealand.

Cells
|June 10, 2022
PubMed

Insights

Corona Virus Disease 2019 (COVID-19) infection may impair epithelial sodium channel (ENaC) function, leading to respiratory distress. This review explores the link between SARS-CoV-2 and ENaC dysfunction in lung fluid balance.

Area of Science:

  • Pulmonary Medicine
  • Virology
  • Cell Biology

Background:

  • COVID-19, caused by SARS-CoV-2, often leads to severe respiratory distress and death.
  • Pulmonary edema and hypoxemia are key symptoms of COVID-19-related respiratory distress.
  • Epithelial sodium channels (ENaC) are crucial for maintaining lung liquid balance and normal function.

Purpose of the Study:

  • To review the implications of SARS-CoV-2 infection on ENaC function.
  • To explore the potential link between viral spike protein and ENaC activity.
  • To connect ENaC dysfunction to COVID-19 symptoms.

Main Methods:

  • Review of existing literature on SARS-CoV-2, ENaC, and furin protease.
  • Analysis of the shared proteolytic cleavage site between viral spike protein and ENaC.
  • Correlation of ENaC function with COVID-19 pathophysiology.

Main Results:

  • Viral spike protein and ENaC share a common cleavage site utilized by furin.
  • Furin cleavage is essential for both ENaC activity and viral spike protein activation.
  • SARS-CoV-2 infection may lead to impaired ENaC activity.

Conclusions:

  • SARS-CoV-2 infection could disrupt lung fluid balance through impaired ENaC function.
  • The shared reliance on furin cleavage suggests a mechanistic link between the virus and ENaC.
  • Understanding this interaction may offer new insights into COVID-19 respiratory complications.

Keywords:
COVID-19SARS-CoV-2airway liquidalveolar liquidepithelial Na+ channelproteasesproteolytic cleavagetransepithelial ion transport

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