查看更多>>摘要：Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic.Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain(RBD).Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood.Here,we dissected the role of N354-linked glycosylation,acquired by BA.2.86 sub-lineages,as a RBD conformational control element in attenuating viral infectivity.The reduced infectivity is recovered in the presence of heparin sulfate,which targets the'N354 pocket'to ease restrictions of conformational transition resulting in a'RBD-up'state,thereby conferring an adjustable infectivity.Furthermore,N354 glycosylation improved spike cleavage and cell-cell fusion,and in particular escaped one subset of ADCC antibodies.Together with reduced immunogenicity in hybrid immunity background,these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.
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