High-mannose N-linked oligosaccharides (High-mannose glycans)

High-mannose N-linked oligosaccharides are a specific class of carbohydrates characterized by a branched structure of mannose residues attached to a chitobiose core, which is linked to asparagine residues on proteins. In the context of viral pathogens like HIV-1, Influenza, and Coronaviruses, these glycans are prominent features of the envelope glycoproteins, such as gp120 or the Spike protein. They are often referred to as the "glycan shield" because they mask protein epitopes from the host's immune system, facilitating immune evasion by preventing the binding of most neutralizing antibodies. Despite this protective role, the dense clusters of high-mannose glycans create unique molecular patterns that can be exploited for therapeutic intervention. Carbohydrate-binding agents, such as the plant-derived lectin Griffithsin or broadly neutralizing antibodies like PGT121, specifically recognize and bind these glycans to neutralize the virus by preventing its entry into host cells. These targets are particularly valuable because glycosylation sites are often more conserved than the underlying protein sequences across different viral strains.

Other names

Oligomannose-type N-glycansHigh-mannose glycansViral envelope glycansMannose-rich N-glycansGlycan shield

Binding to terminal mannose residues on viral glycoproteins to sterically block receptor binding sites or prevent conformational changes required for viral-host membrane fusion.