How the COVID-19 spike protein may cause airway inflammation by affecting the CFTR chloride channel
Official title: COVID-19 airway inflammation is due to Spike inhibition of CFTR signaling
Funded at Henry M. Jackson Fdn for the Adv Mil/med · NIH-11257688 · Data updated 2026-11-12
This project will see if the SARS‑CoV‑2 spike protein makes lungs inflamed by reducing activity of the CFTR chloride channel in human airway cells, which could explain COVID‑19 airway problems.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Henry M. Jackson Fdn for the Adv Mil/med NIH-funded |
| Lab location | 1 site (Bethesda, United States) |
| Project start | January 15, 2023 |
| Project end | December 31, 2026 |
| Funding year | 2026 |
| Award (this year) | $565,490 |
| NIH project number | 5R01HL167048-04 |
| Project ID | NIH-11257688 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with current or recent COVID‑19 and ongoing airway inflammation, and people with cystic fibrosis whose CFTR function is relevant, would be the most directly related patient groups for sample donation or future trials.
✕Less likely to help
People without respiratory infection or whose breathing problems have causes unrelated to CFTR, ACE2, or Spike interactions are unlikely to benefit from this line of work.
What this research studies
Researchers use a human 'lung‑on‑a‑chip' system and cultured human airway cells to look at whether the viral Spike protein binds with ACE2 and reduces CFTR protein and chloride channel activity. They measure downstream effects on inflammatory signaling (NFκB) and sodium channel (ENaC) activation and study how Spike disrupts CFTR recycling to the cell surface. The team also tests whether low doses of cardiac glycoside drugs (ouabain, digitoxin, digoxin) can block Spike:ACE2 binding and rescue CFTR function. Findings come from lab experiments using human‑derived epithelial cells and biochemical methods rather than from a patient drug trial.
Why it matters
Potential benefit: If correct, this could reveal a new reason why COVID‑19 causes airway inflammation and point to existing drugs that might help protect airway function.
How similar studies have gone: Laboratory studies have shown Spike interacts with ACE2 and can alter ion channel signaling and inflammation, and some in vitro work suggests cardiac glycosides block Spike:ACE2 binding, but applying these findings specifically to CFTR loss and airway inflammation is relatively new.
Where this research is happening
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Henry M. Jackson Fdn for the Adv Mil/med
Bethesda, United States Active
Researchers
- Principal investigator: Pollard, Harvey Bruce — Henry M. Jackson Fdn for the Adv Mil/med
- Study coordinator: Pollard, Harvey Bruce
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About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.