High-mannose N-glycan (HMG) (HMG)

High-mannose N-glycans (HMGs) are a class of oligosaccharides characterized by a core of two N-acetylglucosamine residues and five to nine mannose residues (Man5-Man9GlcNAc2). While typically processed into complex glycans in healthy human cells, they are often retained in high density on the surface glycoproteins of enveloped viruses, such as HIV-1 gp120 and the SARS-CoV-2 Spike protein, due to steric hindrance or altered biosynthetic pathways [2.1.1, 2.4.5]. These mannose-rich motifs serve as a "glycan shield" to evade the host immune system but also act as specific attachment factors for host receptors like DC-SIGN [2.1.3, 2.4.5]. Furthermore, aberrant high-mannose glycosylation is a hallmark of certain cancers and is prominently displayed on tumor-derived extracellular vesicles (EVs), making them valuable biomarkers for liquid biopsies [3.2.1, 3.2.3]. Consequently, HMGs have emerged as attractive therapeutic targets for broad-spectrum antivirals and cancer diagnostics [2.4.2, 3.2.2]. Therapeutic agents targeting these motifs include natural lectins like Griffithsin and broadly neutralizing antibodies like 2G12, which bind and neutralize pathogens by blocking entry or inducing aggregation [2.3.1, 2.4.1]. Despite their potential, challenges include the risk of off-target binding to host glycoproteins and the immunogenicity of non-human lectins [2.4.3, 3.3.2].

Other names

Oligomannose-type glycanMannose-rich N-glycan motifMan5-Man9GlcNAc2Trimer-associated mannose-patchTAMPHigh-mannose cluster

Binding to high-mannose glycans blocks viral entry and fusion, prevents attachment to host receptors (e.g., DC-SIGN), and can induce aggregation of viral particles or extracellular vesicles.