Influenza hemagglutinin high-mannose glycans (HA high-mannose glycans)

Influenza hemagglutinin high-mannose glycans are carbohydrate structures covalently attached to the hemagglutinin (HA) protein, the primary surface antigen of the influenza virus. These glycans are essential for the virus as they facilitate correct protein folding and assembly while providing a "glycan shield" that protects conserved viral epitopes from host antibody recognition (Watanabe et al., 2019). Unlike the complex glycans typically found on mature human proteins, these high-mannose structures are often clustered on the viral surface, making them distinct targets for therapeutic intervention. Carbohydrate-binding agents (CBAs), such as the lectins Griffithsin and Cyanovirin-N, specifically recognize and bind to these mannose-rich regions (O'Keefe et al., 2010). This binding effectively neutralizes the virus by sterically blocking its entry into host cells or preventing the fusion of the viral envelope with the endosomal membrane. While promising as broad-spectrum antivirals, targeting these glycans requires careful consideration of potential cross-reactivity with host glycoproteins and the immunogenic nature of the protein-based binders used to target them.

Other names

Hemagglutinin N-glycansHA mannosylated glycansInfluenza HA glycan shieldHigh-mannose N-linked oligosaccharides of HA

Carbohydrate-binding agents (CBAs) bind to the terminal mannose residues of the high-mannose glycans on the hemagglutinin (HA) surface, creating a physical barrier that prevents the virus from attaching to sialic acid receptors on host cells or undergoing the pH-induced conformational change necessary for membrane fusion (O'Keefe et al., 2010; Watanabe et al., 2019).