Basaran, R., Budhadev, D., Dimitriou, E. et al. (7 more authors) (2025) Polyvalent Mannuronic Acid-Coated Gold Nanoparticles for Probing Multivalent Lectin–Glycan Interaction and Blocking Virus Infection. Viruses, 17 (8). 1066. ISSN: 1999-4915
Abstract
Multivalent lectin–glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information remains to be limited for some important MLGIs, significantly restricting the research progress. We have recently demonstrated that functional nanoparticles, including ∼4 nm quantum dots and varying sized gold nanoparticles (GNPs), densely glycosylated with various natural mono- and oligo- saccharides, are powerful biophysical probes for MLGIs. Using two important viral receptors, DC-SIGN and DC-SIGNR (together denoted as DC-SIGN/R hereafter), as model multimeric lectins, we have shown that α-mannose and α-manno-α-1,2-biose (abbreviated as Man and DiMan, respectively) coated GNPs not only can provide sensitive measurement of MLGI affinities but also reveal critical structural information (e.g., binding site orientation and mode) which are important for MLGI targeting. In this study, we produced mannuronic acid (ManA) coated GNPs (GNP-ManA) of two different sizes to probe the effect of glycan modification on their MLGI affinity and antiviral property. Using our recently developed GNP fluorescence quenching assay, we find that GNP-ManA binds effectively to both DC-SIGN/R and increasing the size of GNP significantly enhances their MLGI affinity. Consistent with this, increasing the GNP size also significantly enhances their ability to block DC-SIGN/R-augmented virus entry into host cells. Particularly, ManA coated 13 nm GNP potently block Ebola virus glycoprotein-driven entry into DC-SIGN/R-expressing cells with sub-nM levels of EC50. Our findings suggest that GNP-ManA probes can act as a useful tool to quantify the characteristics of MLGIs, where increasing the GNP scaffold size substantially enhances their MLGI affinity and antiviral potency.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 by the authors. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | mannuronic acid; Ebola virus inhibition; fluorescence quenching; gold nanoparticle; multivalent lectin–glycan interaction |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) |
Funding Information: | Funder Grant number BBSRC (Biotechnology & Biological Sciences Research Council) BB/R007829/1 BBSRC (Biotechnology & Biological Sciences Research Council) BB/Y005856/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 31 Jul 2025 13:40 |
Last Modified: | 31 Jul 2025 13:40 |
Published Version: | https://www.mdpi.com/1999-4915/17/8/1066 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/v17081066 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:229815 |