Characterization and Function of Glycans on the Spike Proteins of SARS-CoV-2 Variants of Concern

• Published in: Microbiology spectrum Vol. 10; no. 6; p. e0312022
• Main Authors: Zheng, Luping, Wang, Ke, Chen, Minghai, Qin, Fujun, Yan, Chuang, Zhang, Xian-En
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 21.12.2022
• Subjects: Antibodies, Neutralizing; Antibodies, Viral; COVID-19; glycosylation pattern; Humans; neutralization; Polysaccharides; receptor binding; Research Article; SARS-CoV-2; SARS-CoV-2 - genetics; Spike Glycoprotein, Coronavirus - genetics; variants of concern; Virology; receptor binding; SARS-CoV-2; variants of concern; neutralization; glycosylation pattern
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.03120-22

SARS-CoV-2 variants of concern (VOCs) pose a great challenge to viral prevention and treatment owing to spike (S) protein mutations, which enhance their infectivity and capacity for immune evasion. However, whether these S protein mutations affect glycosylation patterns and thereby influence infectivity and immunogenicity remains unclear. In this study, four VOC S proteins-S-Alpha, S-Beta, S-Delta, and S-Omicron-were expressed and purified. Lectin microarrays were performed to characterize their glycosylation patterns. Several glycans were differentially expressed among the four VOC S proteins. Furthermore, the functional examination of glycans differentially expressed on S-Omicron revealed a higher expression of fucose-containing glycans, which modestly increased the binding of S-Omicron to angiotensin converting enzyme 2 (ACE2). A higher abundance of sialic acid and galactose-containing glycan was observed on S-Omicron, which significantly reduced its sensitivity against broad S protein-neutralizing antibodies. These findings contribute to the further understanding of SARS-CoV-2 infection mechanisms and provide novel glycan targets for emerging and future variants of SARS-CoV-2. Though glycosylation sites of SARS-CoV-2 S protein remain highly conserved, we confirmed that mutations in the gene affect the S protein glycan expression pattern in different variants. More importantly, we found that glycans were differentially expressed on the S protein of the Omicron variant, enabling different forms of receptor binding and neutralization resistance. This study improves our understanding of SARS-CoV-2 glycomics and glycobiology and provides novel therapeutic and preventive strategies for SARS-CoV-2 VOCs.