High-mannose N-linked glycan (HMG)

High-mannose N-linked glycans are a type of carbohydrate modification found extensively on the surface glycoproteins of enveloped viruses, including HIV-1, SARS-CoV-2, and Ebola. These glycans are characterized by a core of N-acetylglucosamine and multiple mannose residues, often forming a dense glycan shield that masks underlying protein epitopes from the host immune system (Watanabe et al., 2020, Nature Communications). In many viral pathogens, the high density of these glycans prevents host enzymes from processing them into complex forms, leaving a high-mannose patch that is distinct from the more processed glycans found on most host proteins (Doores, 2015, Carbohydrate Research). This unique signature makes them an attractive target for broadly neutralizing antibodies (bNAbs) and lectins, which can bind these clusters to neutralize the virus or trigger immune responses (Walker et al., 2011, Nature). Therapeutic development focuses on using these glycans as targets for vaccines or as docking sites for entry inhibitors to prevent infection and spread. Furthermore, the presence of these glycans is critical for proper protein folding and stability of the viral envelope spikes. Because they are less prevalent on mature human proteins, they offer a degree of selectivity for antiviral intervention.

Other names

Oligomannose glycanHigh-mannose patchMan5-9GlcNAc2Viral glycan shieldHigh-mannose N-linked glycans on enveloped virus glycoproteins

Binding to high-mannose clusters on viral glycoproteins to sterically hinder receptor binding or facilitate immune-mediated clearance.