Open AccessFurin cleavage of the SARS-CoV-2 spike is modulated by O -glycosylation
Author(s) -
Liping Zhang,
Matthew Mann,
Zulfeqhar A. Syed,
Hayley M Reynolds,
E Tian,
N.L. Samara,
Darryl C. Zeldin,
Lawrence A. Tabak,
Karl S. Hagen
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2109905118
Subject(s) - furin , cleavage (geology) , infectivity , glycosylation , syncytium , biology , virology , mutant , chemistry , virus , genetics , biochemistry , gene , enzyme , paleontology , fracture (geology)
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 thatO -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 decreaseO -glycosylation, which increases furin cleavage and syncytia formation. Our results highlight how host-mediatedO -glycosylation may influence viral infectivity and how mutations in the recent alpha and delta variants may circumvent this.