Targeting spike glycans to inhibit SARS-CoV2 viral entry

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  • Guseman, Alex J.
    • Other Affiliation: University of Pittsburgh
  • Rennick, Linda J.
    • Other Affiliation: University of Pittsburgh
  • Nambulli, Sham
    • Other Affiliation: University of Pittsburgh
  • Roy, Chandra N.
    • Other Affiliation: University of Pittsburgh
  • Martinez, David R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Yang, Darian T.
    • Other Affiliation: University of Pittsburgh
  • Bhinderwala, Fatema
    • Other Affiliation: University of Pittsburgh
  • Vergara, Sandra
    • Other Affiliation: University of Pittsburgh
  • Schaefer, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Ambrose, Zandrea
    • Other Affiliation: University of Pittsburgh
  • Duprex, W. Paul
    • Other Affiliation: University of Pittsburgh
  • Gronenborn, Angela M.
    • Other Affiliation: University of Pittsburgh
Abstract
  • SARS-CoV-2 spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety of biophysical approaches, we demonstrate that the interaction is avidity driven and that BOA cross-links the spike protein into soluble aggregates. Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that multivalent glycan-targeting molecules have the potential to act as pan-coronavirus inhibitors.
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  • Article
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  • Attribution-NonCommercial-NoDerivs 4.0 International
Journal title
  • Proceedings of the National Academy of Sciences of the United States of America
Journal volume
  • 120
Journal issue
  • 38
Page start
  • e2301518120
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  • English
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  • Publisher
ISSN
  • 1091-6490

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