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Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection

Author

Listed:
  • Simon J. L. Petitjean

    (Université catholique de Louvain)

  • Wenzhang Chen

    (Laboratory of Bio-Organic Chemistry (NARILIS), UNamur)

  • Melanie Koehler

    (Université catholique de Louvain)

  • Ravikumar Jimmidi

    (Laboratory of Bio-Organic Chemistry (NARILIS), UNamur)

  • Jinsung Yang

    (Université catholique de Louvain)

  • Danahe Mohammed

    (Université catholique de Louvain)

  • Blinera Juniku

    (Université catholique de Louvain)

  • Megan L. Stanifer

    (Medical Faculty, Center for Integrative Infectious Diseases Research (CIID), University of Heidelberg
    College of Medicine, University of Florida)

  • Steeve Boulant

    (Medical Faculty, Center for Integrative Infectious Diseases Research (CIID), University of Heidelberg
    College of Medicine, University of Florida)

  • Stéphane P. Vincent

    (Laboratory of Bio-Organic Chemistry (NARILIS), UNamur)

  • David Alsteens

    (Université catholique de Louvain
    Walloon Excellence in Life sciences and Biotechnology (WELBIO))

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.

Suggested Citation

  • Simon J. L. Petitjean & Wenzhang Chen & Melanie Koehler & Ravikumar Jimmidi & Jinsung Yang & Danahe Mohammed & Blinera Juniku & Megan L. Stanifer & Steeve Boulant & Stéphane P. Vincent & David Alsteen, 2022. "Multivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30313-8
    DOI: 10.1038/s41467-022-30313-8
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    References listed on IDEAS

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    1. Melanie Koehler & Pavithra Aravamudhan & Camila Guzman-Cardozo & Andra C. Dumitru & Jinsung Yang & Serena Gargiulo & Patrice Soumillion & Terence S. Dermody & David Alsteens, 2019. "Glycan-mediated enhancement of reovirus receptor binding," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Xiaoli Xiong & Peter J. Coombs & Stephen R. Martin & Junfeng Liu & Haixia Xiao & John W. McCauley & Kathrin Locher & Philip A. Walker & Patrick J. Collins & Yoshihiro Kawaoka & John J. Skehel & Steven, 2013. "Receptor binding by a ferret-transmissible H5 avian influenza virus," Nature, Nature, vol. 497(7449), pages 392-396, May.
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