Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12
Name
s41598-022-06157-z.pdf
Description
Published version
Size
2.02 MB
Format
Adobe PDF
Checksum (MD5)
0e20a92a50b1f4417246038969185725
Author(s)
Miller, Nathaniel L
Subramanian, Vidya
Clark, Thomas
Raman, Rahul
Sasisekharan, Ram
Date Issued
2022
Journal
Scientific Reports
Publisher
Springer Science and Business Media LLC
Citation
Miller, Nathaniel L, Subramanian, Vidya, Clark, Thomas, Raman, Rahul and Sasisekharan, Ram. 2022. "Conserved topology of virus glycoepitopes presents novel targets for repurposing HIV antibody 2G12." Scientific Reports, 12 (1).
Version
Final published version
Abstract
AbstractComplex 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41598-022-06157-Z
