Functional analysis of polymorphisms at the S1/S2 site of SARS-CoV-2 spike protein.

Autor:	Arora, Prerna, Sidarovich, Anzhalika, Graichen, Luise, Hörnich, Bojan, Hahn, Alexander, Hoffmann, Markus, Pöhlmann, Stefan
Předmět:	SARS-CoV-2 Omicron variant FUNCTIONAL analysis SARS-CoV-2 CELL fusion VIRAL mutation VIRAL tropism
Zdroj:	PLoS ONE; 3/25/2022, Vol. 17 Issue 3, p1-16, 16p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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