Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 16, 2026 42 minutes ago
A scientific review focuses on ion channels and virus-made membrane proteins that may help SARS-CoV-2 replicate, disrupt cells, provoke inflammation and possibly contribute to persistent illness.
SARS-CoV-2 viroporins, particularly the E protein, may disrupt cellular ion balance and expose new
therapeutic targets
Researchers Faisal F. Alousi and Abdel A. Alli examined evidence surrounding viroporins—viral proteins that alter membranes and their role in COVID-19. The researchers are from the University of Florida College of Medicine’s Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, and Department of Physiology and Aging. Alousi is also affiliated with the Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University in Dammam, Saudi Arabia.
E protein emerges as the stronger ion-channel candidate
The review distinguishes between viroporins and true ion channels. A viroporin can make membranes more permeable, while a canonical ion channel should demonstrate selective ion movement, measurable conductance and gating behavior.
Among SARS-CoV-2 proteins, the envelope, or E, protein has the stronger evidence for channel activity. Electrophysiological studies support membrane conductance and cation selectivity, while mutations in its transmembrane region affect ion transport and viral functions. However, its complete single-channel behavior and gating remain incompletely defined. Evidence that Orf3a behaves as a bona fide ion channel is less consistent.
How disturbed ions could amplify disease
This
Thailand Medical News report highlights how changes in ion movement could have wide biological consequences. E-protein activity can disturb calcium homeostasis in the endoplasmic reticulum-Golgi network, potentially promoting cellular stress, altered autophagy and NLRP3 inflammasome activation.
The review also describes effects involving sodium, chloride and potassium balance. One focus is the epithelial sodium channel, ENaC, which helps move sodium and water from lung airspaces. SARS-CoV-2 may interfere with ENaC activation and function, potentially reducing alveolar fluid clearance and contributing to fluid accumulation and impaired oxygen exchange.
Viroporins may also weaken lysosomal acidification, potentially compromising antigen processing and immune responses. Meanwhile, calcium dysregulation may indirectly damage mitochondria, increasing oxidative stress and inflammatory signaling, although direct evidence that E protein physically interacts with mitochondria remains limited.
Viral proteins may spread beyond infected cells
Another mechanism involves extracellular vesicles. Evidence reviewed indicates that infected cells can release membrane vesicles containing coronavirus E protein. These vesicles could carry viroporins into neighboring cells, potentially extending membrane disruption beyond cells directly infected through ACE2 or NRP1 receptors.
The authors also discuss SARS-CoV-2 material pers
isting in lungs, gastrointestinal tissue and lymphoid organs after acute infection, while stressing that this represents persistence rather than classical viral latency. Whether viroporins materially drive long COVID remains an unanswered question.
Conclusions
The evidence positions SARS-CoV-2 viroporins as important contributors to disrupted ion balance, cellular stress, inflammation and viral propagation, with the E protein supported more strongly than Orf3a. Future research must establish which channel activities are reproducible and druggable, while testing selective inhibitors and determining whether viral proteins can compensate when one viroporin is blocked.
The study findings were published in the peer reviewed journal: Viruses.
https://www.mdpi.com/1999-4915/18/9/1027 
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