SARS-CoV-2 spike (S) glycoprotein high-mannose glycans (SARS-CoV-2 S high-mannose glycans)

The SARS-CoV-2 spike (S) glycoprotein is extensively modified by N-linked glycans, which play a critical role in the virus's life cycle (Watanabe et al., Science, 2020). A significant portion of these glycans are of the high-mannose (oligomannose) type, which are less processed than the complex glycans typically found on mature human cell surface proteins. These high-mannose clusters, particularly at sites like N234, are essential for stabilizing the receptor-binding domain (RBD) in the "up" conformation required for binding to the host ACE2 receptor (Casalino et al., ACS Central Science, 2020). Furthermore, these glycans form a "glycan shield" that protects the underlying protein epitopes from neutralizing antibodies, facilitating immune evasion. Because these high-mannose structures are distinct and relatively dense on the viral surface, they serve as therapeutic targets for mannose-binding lectins and specific glycan-targeting antibodies (Cai et al., Science, 2020). Drugs like Griffithsin can bind these glycans to potently inhibit viral entry, making them candidates for broad-spectrum antiviral interventions (O'Keefe et al., Journal of Virology, 2010).

Other names

SARS-CoV-2 S protein oligomannose glycansN-linked high-mannose glycans of Spike proteinSpike protein glycan shieldSARS-CoV-2 S high-mannose clusters

Binding to high-mannose glycans on the spike protein surface to sterically hinder interaction with the ACE2 receptor or to prevent the conformational changes required for viral fusion (Cai et al., Science, 2020).