SARS-CoV-2 can recruit the host protein phosphatase 2A (PP2A) and it manipulates by it the host’s antiviral responses.(1) With the help of PP2A the virus can overactivate cofilin, the actin severing protein, because manipulated and overactivated PP2A can dephosphorulate and so overactivate cofilin. (2) By overactivating cofilin the virus can overactivate the macrophages of the central nervous system, the microglia and possibly the macrophages of the body and induce them to increase the production of cytokines and this way the virus orchestrates a full blown cytokine storm. (3)(4) Overactivated cofilin can also injure intestinal epithelial junctions and increase intestinal permeability and sart exaggerated inflammation.(5) Proinsulin C-peptide stimulates phosphorylation of PAK, LIMK and cofilin downstream of Rac-1 and Cdc42, leading to cofilin inactivation and actin filament stabilization. This may prevent that the virus overactivates cofilin in the immune cells ad possibly in the cells responsible for maintaining barrier functions generally in the body (6)(7) C-peptide by stimulating Rac1 may activate SET and so inhibit PP2A.(8) According to recent autopsy findings alveolar macrophages have a prominent role in causing the damages of SARS-CoV-2 infection.(9) It is alarming that mechanical ventilation may increase macrophage activation and inflammation also and so may cause a second hit for the lungs and increase further the systemic cytokine storm.(10) Gastrointestinal injury seems to be common in critically ill COVID-19 patients increasing the plausibility that the virus is able to damage the tight junctions.(11)
1. https://www.biorxiv.org/content/10.1101/2020.04.01.020941v1
2. https://pubmed.ncbi.nlm.nih.gov/11093160/
3. https://pubmed.ncbi.nlm.nih.gov/28194647/
4. https://pubmed.ncbi.nlm.nih.gov/22558315/
5. https://pubmed.ncbi.nlm.nih.gov/26878213/
6. https://pubmed.ncbi.nlm.nih.gov/19373435/
7. https://pubmed.ncbi.nlm.nih.gov/7821746/
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783461/
9. https://www.researchsquare.com/article/rs-19346/v1?fbclid=IwAR3a0_6Q33ZWKc5G0HB6iiz58XOzHs-zVySreKiCNUfcnQjcLUlv20Hpfqs
10. https://www.researchgate.net/publication/6908266_Alveolar_macrophages_contribute_to_alveolar_barrier_dysfunction_in_ventilator-induced_lung_injury?fbclid=IwAR2Wp6QT5x7dvicL3wTwrsDUKsC_buS9vjut9Zeuci7VZPHgk9QVcuF8G4A
11. https://www.medrxiv.org/content/10.1101/2020.03.25.20043570v1.full.pdf?fbclid=IwAR1x6qwugJGhwvKNHoFa0sWdzSPyJ7YmcMYLjtpDTGtRvlDwYdYX4lS75LY