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Targeting spike glycans to inhibit SARS-CoV2 viral entry

2023; National Academy of Sciences; Volume: 120; Issue: 38 Linguagem: Inglês

10.1073/pnas.2301518120

1091-6490

Alex J. Guseman, Linda J. Rennick, Sham Nambulli, Chandra Nath Roy, David R. Martinez, Darian T. Yang, Fatema Bhinderwala, Sandra Vergara, Alexandra Schaefer, Ralph S. Baric, Zandrea Ambrose, W. Paul Duprex, Angela M. Gronenborn,

Complement system in diseases

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.