ArticleAmerican journal of physiology. Lung cellular and molecular physiology2009
SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms.
Article in American journal of physiology. Lung cellular and molecular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins.Viruses · 2025Review
- ENaC gene variants and their involvement in Covid‑19 severity.Biomedical reports · 2024Article
- A Review of Epithelial Ion Transporters and Their Roles in Equine Infectious Colitis.Veterinary sciences · 2024Review
- Effect of SARS-CoV-2 S protein on the proteolytic cleavage of the epithelial Na+ channel ENaC.PloS one · 2024Article
- The controversial effect of smoking and nicotine in SARS-CoV-2 infection.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Review
- In Vitro and In Vivo Therapeutic Potential of 6,6'-Dihydroxythiobinupharidine (DTBN) fromInternational journal of molecular sciences · 2023Article
- Is intestinal transport dysfunctional in COVID-19-related diarrhea?American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Potent NKT cell ligands overcome SARS-CoV-2 immune evasion to mitigate viral pathogenesis in mouse models.PLoS pathogens · 2023Article
- Direct endothelial ENaC activation mitigates vasculopathy induced by SARS-CoV2 spike protein.Frontiers in immunology · 2023Article
- Protein Kinase C Inhibitors Reduce SARS-CoV-2 Replication in Cultured Cells.Microbiology spectrum · 2022Article
- Understanding COVID-19 susceptibility and presentation based on its underlying physiology.Physiological reviews · 2022Article
- COVID-19 and Liquid Homeostasis in the Lung-A Perspective through the Epithelial Sodium Channel (ENaC) Lens.Cells · 2022Review
- SARS-CoV-2, Zika viruses and mycoplasma: Structure, pathogenesis and some treatment options in these emerging viral and bacterial infectious diseases.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- COVID-19: the CaMKII-like system of S protein drives membrane fusion and induces syncytial multinucleated giant cells.Immunologic research · 2021Article
- Bisindolylmaleimide IX: A novel anti-SARS-CoV2 agent targeting viral main protease 3CLpro demonstrated by virtual screening pipeline and in-vitro validation assays.Methods (San Diego, Calif.) · 2021Article
- Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells.ACS pharmacology & translational science · 2021Article
- Regulation of epithelial sodium channel activity by SARS-CoV-1 and SARS-CoV-2 proteins.Biophysical journal · 2021Article
- Molecular mechanisms of Na,K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- G-Protein-Coupled Receptor and Ion Channel Genes Used by Influenza Virus for Replication.Journal of virology · 2021Article
- SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport.American journal of physiology. Lung cellular and molecular physiology · 2021Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Among the multiple organ disorders caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia is the most serious and often fatal event. We hypothesized that two of the hydrophilic structural coronoviral proteins (S and E) would regulate alveolar fluid clearance by decreasing the cell surface expression and activity of amiloride-sensitive epithelial sodium (Na(+)) channels (ENaC), the rate-limiting protein in transepithelial Na(+) vectorial transport across distal lung epithelial cells. Coexpression of either S or E protein with human alpha-, beta-, and gamma-ENaC in Xenopus oocytes led to significant decreases of both amiloride-sensitive Na(+) currents and gamma-ENaC protein levels at their plasma membranes. S and E proteins decreased the rate of ENaC exocytosis and either had no effect (S) or decreased (E) rates of endocytosis. No direct interactions among SARS-CoV E protein with either alpha- or gamma-ENaC were indentified. Instead, the downregulation of ENaC activity by SARS proteins was partially or completely restored by administration of inhibitors of PKCalpha/beta1 and PKCzeta. Consistent with the whole cell data, expression of S and E proteins decreased ENaC single-channel activity in oocytes, and these effects were partially abrogated by PKCalpha/beta1 inhibitors. Finally, transfection of human airway epithelial (H441) cells with SARS E protein decreased whole cell amiloride-sensitive currents. These findings indicate that lung edema in SARS infection may be due at least in part to activation of PKC by SARS proteins, leading to decreasing levels and activity of ENaC at the apical surfaces of lung epithelial cells.
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