Figure legends:
  1. SARS-CoV-2 binding: the increase in the pH of Trans-Golgi network may alter hACE2 glycosilation. Azithromycin resulted in a ganglioside-mimic given its similar volume and analogous chemical features than GM1. Since the spike protein of SARS-CoV-2 displays a ganglioside-binding site, azithromycin might inhibit SARS-CoV-2 infection by binding to this site. It may also interfere with ligand CD147 receptor interactions.
  2. Membrane fusion, endocytosis, and lysosomal protease activation: the increase in lysosomal pH impairs the endocytosis process and the action of essential lysosomal proteases, as cathepsins or furins, implicated in the cleavage of the spike protein of SARS-CoV-2.
  3. Reduction of pro-inflammatory cytokines and chemokines production: (IL-1β, IL-6, IL-8, IL-12, IFN-γ, IP-10, TNF-α, and GM-CSF).
  4. Lymphocytes: suppression of CD4+ T-cell activation.
  5. Alveolar macrophages: shift in the polarization to anti-inflammatory phenotype and increase apoptosis.
  6. Fibroblasts: antifibrotic activity: inhibition of fibroblast proliferation, collagen production reduction, decrease transforming growth factor TGF-β production, inhibition of TGF-β induced pro-fibrotic gene stimulation.
  7. Epithelial cells: stabilization of the cell membrane, increase in the transepithelial electrical barrier and induction of the processing of the tight junction proteins claudins and junctional adhesion molecule-A. Decrease mucus hypersecretion, which may improve mucociliary clearance.