Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12.
Sci Rep
; 12(1): 2594, 2022 02 16.
Article
in English
| MEDLINE | ID: covidwho-1692553
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
HIV Antibodies
/
Models, Immunological
/
Influenza A Virus, H1N1 Subtype
/
Influenza A Virus, H3N2 Subtype
/
Broadly Neutralizing Antibodies
/
SARS-CoV-2
/
Antibodies, Monoclonal
Type of study:
Diagnostic study
/
Randomized controlled trials
Limits:
Animals
/
Humans
Language:
English
Journal:
Sci Rep
Year:
2022
Document Type:
Article
Affiliation country:
S41598-022-06157-z
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