Nanostructured glycan architecture is important in the inhibition of influenza A virus infection
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Authors
Kwon, Seok Joon
Na, Dong Hee
Kwak, Jong Hwan
Douaisi, Marc
Zhang, Fuming
Park, Eun Ji
Park, Jong Hwan
Youn, Hana
Song, Chang Seon
Kane, Ravi S.
Issue Date
2017-01-10
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Rapid change and zoonotic transmission to humans have enhanced the virulence of the influenza A virus (IAV)3. Neutralizing antibodies fail to provide lasting protection from seasonal epidemics1,4. Furthermore, the effectiveness of anti-influenza neuraminidase inhibitors has declined because of drug resistance5. Drugs that can block viral attachment and cell entry independent of antigenic evolution or drug resistance might address these problems. We show that multivalent 6′-sialyllactose-polyamidoamine (6SL–PAMAM) conjugates, when designed to have well-defined ligand valencies and spacings, can effectively inhibit IAV infection. Generation 4 (G4) 6SL–PAMAM conjugates with a spacing of around 3 nm between 6SL ligands (S3–G4) showed the strongest binding to a hemagglutinin trimer (dissociation constant of 1.6 × 10−7 M) and afforded the best inhibition of H1N1 infection. S3–G4 conjugates were resistant to hydrolysis by H1N1 neuraminidase. These conjugates protected 75% of mice from a lethal challenge with H1N1 and prevented weight loss in infected animals. The structure-based design of multivalent nanomaterials, involving modulation of nanoscale backbone structures and number and spacing between ligands, resulted in optimal inhibition of IAV infection. This approach may be broadly applicable for designing effective and enduring therapeutic protection against human or avian influenza viruses.
Description
Nature Nanotechnology, 12, 48-56
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Nanostructured glycan architecture is important in the inhibition of influenza A virus infection, S.-J. Kwon, D. H. Na, J. H. Kwak, M. Douaisi, F. Zhang, E. J. Park, J.-H. Park, H. Youn, C.-S. Song, R. S. Kane, J. S. Dordick, K. B. Lee, R. J. Linhardt, Nature Nanotechnology, 12, 48-56, 2017.
Publisher
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
17483395
17483387
17483387