The COVID-19 Cell Signalling Problem: Spike, RAGE, PKC, p38, NFκB & IL-6 Hyper-Expression and the Human Ezrin Peptide, VIP, PKA-CREB Solution

SARS-CoV-2 infection inhibits interferon expression, while hyper-activating innate-immune signalling and expression of pro-inflammatory cytokines. proteins: Spike, M nsp6, nsp12 nsp13 inhibit IFR3-mediated Type-1-interferon defence, but hyper-activate intracellular signalling, which leads to dysfunctional cytokines, particularly IL-1β IL-6, IL-8, TNFα. Ezrin, a sub-membrane adaptor-protein, organises multi-protein-complexes such as ezrin+NHERF1+NHE+CFTR, control the density location ACE2 receptor on luminal surface airway-epithelial-cells, well determining susceptibility infection. This protein complex is vital for lung-surfactant production efficient gas-exchange. Ezrin also forms that regulate kinases; Ras, PKC, PI3K, PKA. m-RAGE pattern-recognition-receptor innate immune system triggered by AGEs, are chemically modified proteins common in elderly obese. multi-protein complexes with ezrin TIRAP, toll-like-receptor adaptor-protein. The main cause COVID-19 not viral p38MAPK mediated TLRs RAGE. In contrast, it appears activated ezrin+PKA results activation transcription-factor CREB, suppresses NFκB cytokine expression. addition, competition between TIRAP form membrane PIP2-lipid-rafts macromolecular-switch changes priority from programs adaptive programs. Human Vasoactive Intestinal Peptide (VIP), Peptides (HEP-1 RepG3) probably activating ras>Raf>MEK>ERK>RSK>CREB>IL-10 favours immunity inhibition innate-inflammation, COVID-19. HEP-1, RepG3, VIP individual human volunteers small clinical studies have been shown be effective therapies, seem closely related mechanism action.