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National Institute of Environmental Health Sciences

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Publication Detail

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

Authors: Miller, Nathaniel L; Subramanian, Vidya; Clark, Thomas; Raman, Rahul; Sasisekharan, Ram

Published In Sci Rep, (2022 Feb 16)

Abstract: 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.

PubMed ID: 35173180 Exiting the NIEHS site

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*

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