Abstract
The recent emergence of highly transmissible SARS-CoV-2 variants illustrates the urgent need to better understand the molecular details of the virus binding to its host cell and to develop anti-viral strategies. While many studies focused on the role of the angiotensin-converting enzyme 2 receptor in the infection, others suggest the important role of cell attachment factors such as glycans. Here, we use atomic force microscopy to study these early binding events with the focus on the role of sialic acids (SA). We show that SARS-CoV-2 binds specifically to 9-O-acetylated-SA with a moderate affinity, supporting its role as an attachment factor during virus landing to cell host surfaces. For therapeutic purposes and based on this finding, we have designed novel blocking molecules with various topologies and carrying a controlled number of SA residues, enhancing affinity through a multivalent effect. Inhibition assays show that the AcSA-derived glycoclusters are potent inhibitors of cell binding and infectivity, offering new perspectives in the treatment of SARS-CoV-2 infection.
| Original language | English |
|---|---|
| Article number | 2564 |
| Journal | Nature Communications |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 2022 |
Funding
We thank you Gert Zimmer (Switzerland) for the VSV S-pseudotyped system. This work was supported by the Université catholique de Louvain, the Foundation Louvain and the Fonds National de la Recherche Scientifique (FRS-FNRS). This project received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 758224) and from the FNRS-Welbio (Grant # CR-2019S-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. S.J.L.P., M.K., and D.A. are Research Fellow, postdoctoral researcher, and Research Associate at the FNRS, respectively. W.C. and S.P.V. are grateful to China Scholarship Council. R.J. received a post-doctoral fellowship from FNRS. S.B. was supported by the German Research Foundation (DFG) project numbers 415089553 (Heisenberg program), 240245660 (SFB1129), the state of Baden-Württemberg (AZ: 33.7533.-6-21/5/1), the Bundesministerium für Bildung und Forschung (BMBF) (01KI20198A) and within the Network University Medicine - Organo-Strat COVID-19. M.L.S. was supported by the BMBF (01KI20239B) and DFG project 416072091.
