Figure legends:
- 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.
- 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.
- 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).
- Lymphocytes: suppression of CD4+ T-cell activation.
- Alveolar macrophages: shift in the polarization to
anti-inflammatory phenotype and increase apoptosis.
- 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.
- 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.