RT Journal Article
SR Electronic
T1 The N764K and N856K mutations in SARS-CoV-2 Omicron BA.1 S protein generate potential cleavage sites for SKI-1/S1P protease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.21.477298
DO 10.1101/2022.01.21.477298
A1 Halim Maaroufi
YR 2022
UL http://biorxiv.org/content/early/2022/01/28/2022.01.21.477298.abstract
AB Spike (S) protein is a key protein in coronaviruses life cycle. SARS-CoV-2 Omicron BA.1 variant of concern (VoC) presents an exceptionally high number of 30 substitutions, 6 deletions and 3 insertions in the S protein. Recent works revealed major changes in the SARS-CoV-2 Omicron biological properties compared to earlier variants of concern (VoCs). Here, 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. The new sites where SKI-1/S1P could cleave S protein might impede the exposition of the internal fusion peptide for membrane fusion and syncytia formation. 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 and nasopharynx. This may explain why Omicron has change of tissue tropism. 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.Competing Interest StatementThe authors have declared no competing interest.