Furin cleavage of the SARS-CoV-2 spike is modulated by <i>O</i> -glycosylation

Abstract

Significance The novel SARS-CoV-2 coronavirus that is responsible for the global pandemic contains a unique insertion of four amino acids within the spike protein (S). Furin cleavage at this novel insertion site has been shown to increase pseudoviral infectivity and syncytia formation. Here we show that O -glycosylation by certain GALNT family members decreases furin cleavage of S and decreases syncytia formation. Moreover, we show that P681 mutations found in the highly transmissible alpha and delta variants decrease O -glycosylation, which increases furin cleavage and syncytia formation. Our results highlight how host-mediated O -glycosylation may influence viral infectivity and how mutations in the recent alpha and delta variants may circumvent this.