Functional analysis of polymorphisms at the S1/S2 site of SARS-CoV-2 spike protein
2022 | journal article. A publication with affiliation to the University of Göttingen.
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Details
- Authors
- Arora, Prerna; Sidarovich, Anzhalika; Graichen, Luise; Hörnich, Bojan; Hahn, Alexander; Hoffmann, Markus; Pöhlmann, Stefan
- Editors
- Bogyo, Matthew
- Abstract
- Several SARS-CoV-2 variants emerged that harbor mutations in the surface unit of the viral spike (S) protein that enhance infectivity and transmissibility. Here, we analyzed whether ten naturally-occurring mutations found within the extended loop harboring the S1/S2 cleavage site of the S protein, a determinant of SARS-CoV-2 cell tropism and pathogenicity, impact S protein processing and function. None of the mutations increased but several decreased S protein cleavage at the S1/S2 site, including S686G and P681H, the latter of which is found in variants of concern B.1.1.7 (Alpha variant) and B.1.1.529 (Omicron variant). None of the mutations reduced ACE2 binding and cell-cell fusion although several modulated the efficiency of host cell entry. The effects of mutation S686G on viral entry were cell-type dependent and could be linked to the availability of cathepsin L for S protein activation. These results show that polymorphisms at the S1/S2 site can modulate S protein processing and host cell entry.
- Issue Date
- 2022
- Journal
- PLoS One
- eISSN
- 1932-6203
- Language
- English