Why #Omicron VOC has predilection for upper airways? Why 🫁 are comparatively spared in Omicron infection?
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Recent works revealed major changes in the #Omicron biological properties (the impairment of cell surface entry & syncytia formation) compared to earlier VoCs. These major changes could be explained, at least in part, by the mutations #N764K and/or #N856K in S2 subunit. 
These mutations were not previously detected in other VoCs. #N764K and #N856K generate two potential cleavage sites for SKI-1/S1P serine protease, known to cleave viral envelope glycoproteins. 3/
The new sites where SKI-1/S1P could cleave Spike protein might impede the exposition of the internal fusion peptide for membrane fusion & syncytia formation. 4/
Based on the human protein atlas, SKI-1/S1P protease is not found in lung tissues (alveolar cells type I/II and endothelial cells), but present in bronchus & nasopharynx. This may explain why Omicron has change of tissue tropism. 5/
Viruses have evolved to use several host proteases for cleavage/activation of envelope glycoproteins.
Mutations that allow viruses to change of protease may have a strong impact in host range, cell and tissue tropism, and pathogenesis. 6/
biorxiv.org/content/10.110…
Mutations that allow viruses to change of protease may have a strong impact in host range, cell and tissue tropism, and pathogenesis. 6/
biorxiv.org/content/10.110…
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