Budhadev, D, Hooper, J, Rocha, C et al. (7 more authors) (2023) A Polyvalent Nano-Lectin Potently Neutralizes SARS-CoV-2 by Targeting Glycans on the Viral Spike Protein. JACS Au, 3 (6). pp. 1755-1766. ISSN 2691-3704
Abstract
Mutations in spike (S) protein epitopes allow SARS-CoV-2 variants to evade antibody responses induced by infection and/or vaccination. In contrast, mutations in glycosylation sites across SARS-CoV-2 variants are very rare, making glycans a potential robust target for developing antivirals. However, this target has not been adequately exploited for SARS-CoV-2, mostly due to intrinsically weak monovalent protein–glycan interactions. We hypothesize that polyvalent nano-lectins with flexibly linked carbohydrate recognition domains (CRDs) can adjust their relative positions and bind multivalently to S protein glycans, potentially exerting potent antiviral activity. Herein, we displayed the CRDs of DC-SIGN, a dendritic cell lectin known to bind to diverse viruses, polyvalently onto 13 nm gold nanoparticles (named G13-CRD). G13-CRD bound strongly and specifically to target glycan-coated quantum dots with sub-nM Kd. Moreover, G13-CRD neutralized particles pseudotyped with the S proteins of Wuhan Hu-1, B.1, Delta variant and Omicron subvariant BA.1 with low nM EC50. In contrast, natural tetrameric DC-SIGN and its G13 conjugate were ineffective. Further, G13-CRD potently inhibited authentic SARS-CoV-2 B.1 and BA.1, with <10 pM and <10 nM EC50, respectively. These results identify G13-CRD as the 1st polyvalent nano-lectin with broad activity against SARS-CoV-2 variants that merits further exploration as a novel approach to antiviral therapy.
Metadata
Authors/Creators: |
|
||||
---|---|---|---|---|---|
Copyright, Publisher and Additional Information: | © 2023 The Authors. Published by American Chemical Society. This is an open access article published 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: | antiviral, polyvalent nano-lectin, SARS-CoV-2, glycan, multivalency | ||||
Dates: |
|
||||
Institution: | The University of Leeds | ||||
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Inorganic Chemistry (Leeds) | ||||
Funding Information: |
|
||||
Depositing User: | Symplectic Publications | ||||
Date Deposited: | 01 Jun 2023 14:13 | ||||
Last Modified: | 17 Aug 2023 10:47 | ||||
Published Version: | https://pubs.acs.org/doi/10.1021/jacsau.3c00163 | ||||
Status: | Published | ||||
Publisher: | American Chemical Society | ||||
Identification Number: | https://doi.org/10.1021/jacsau.3c00163 |
Downloads
Filename: Manu-Final-clean_Dejian Zhou.pdf
Licence: CC-BY 4.0
Filename: Revised SI-Final_Dejian Zhou.pdf
Licence: CC-BY 4.0