Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12

Sci Rep. 2022 Feb 16;12(1):2594. doi: 10.1038/s41598-022-06157-z.


Complex glycans decorate viral surface proteins and play a critical role in virus-host interactions. Viral surface glycans shield vulnerable protein epitopes from host immunity yet can also present distinct "glycoepitopes" that can be targeted by host antibodies such as the potent anti-HIV antibody 2G12 that binds high-mannose glycans on gp120. Two recent publications demonstrate 2G12 binding to high mannose glycans on SARS-CoV-2 and select Influenza A (Flu) H3N2 viruses. Previously, our lab observed 2G12 binding and functional inhibition of a range of Flu viruses that include H3N2 and H1N1 lineages. In this manuscript, we present these data alongside structural analyses to offer an expanded picture of 2G12-Flu interactions. Further, based on the remarkable breadth of 2G12 N-glycan recognition and the structural factors promoting glycoprotein oligomannosylation, we hypothesize that 2G12 glycoepitopes can be defined from protein structure alone according to N-glycan site topology. We develop a model describing 2G12 glycoepitopes based on N-glycan site topology, and apply the model to identify viruses within the Protein Data Bank presenting putative 2G12 glycoepitopes for 2G12 repurposing toward analytical, diagnostic, and therapeutic applications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism*
  • Broadly Neutralizing Antibodies / metabolism*
  • Dogs
  • Drug Repositioning
  • Epitopes
  • HIV Antibodies / metabolism*
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H1N1 Subtype / metabolism
  • Influenza A Virus, H3N2 Subtype / immunology*
  • Influenza A Virus, H3N2 Subtype / metabolism
  • Madin Darby Canine Kidney Cells
  • Models, Immunological*
  • Molecular Targeted Therapy
  • Neutralization Tests
  • Polysaccharides / metabolism
  • SARS-CoV-2 / immunology*


  • 2G12 monoclonal antibody
  • Antibodies, Monoclonal
  • Broadly Neutralizing Antibodies
  • Epitopes
  • H1N1 virus hemagglutinin
  • HIV Antibodies
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Polysaccharides