Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry
Guseman, A. J.; Rennick, L. J.; Nambulli, S.; Roy, C. N.; Martinez, D.; Yang, D. T.; Bhinderwhala, F.; Vergara, S.; Baric, R. S.; Ambrose, Z.; Duprex, W. P.; Gronenborn, A. M.
Show 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 tools, we demonstrate that the interaction is avidity driven and that BOA crosslinks 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 glycan-targeting molecules have the potential to be pan-coronavirus inhibitors.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Deamidation drives molecular aging of the SARS-CoV-2 spike receptor-binding motif 96%
- Molecular architecture and domain arrangement of the placental malaria protein VAR2CSA suggests a model for receptor binding 95%
- A Conserved Core Region of the Scaffold NEMO is Essential for Signal-induced Conformational Change and Liquid-liquid Phase Separation 95%
Similar papers in this journal
- SARS-CoV-2 spike glycosylation affects function and neutralization sensitivity 97%
- Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission 96%
- A combination of RBD and NTD neutralizing antibodies limits the generation of SARS-CoV-2 spike neutralization-escape mutants 96%
Similar papers in this journal
- Asymmetric structures and conformational plasticity of the uncleaved full-length human immunodeficiency virus (HIV-1) envelope glycoprotein trimer 96%
- The Sequence Basis for Selectivity of Ephrin-B2 Ligand for Eph Receptors and Pathogenic Henipavirus G Glycoproteins 96%
- A derivative of the D5 monoclonal antibody that targets the gp41 N-heptad repeat of HIV-1 with broad tier-2 neutralizing activity 96%
Similar papers in this journal
- The Q226L mutation can convert a highly pathogenic H5 2.3.4.4e virus to bind human-type receptors 96%
- IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding 96%
- Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages 96%
Similar papers in this journal
- Intranasal administration of a monoclonal neutralizing antibody protects mice against SARS-CoV-2 infection 96%
- Divide et Impera: Identification of Small-Molecule Inhibitors of HCMV Replication Interfering with Dimerization of DNA Polymerase Processivity Factor UL44 95%
- Crystal Structure of a Retroviral Polyprotein:Prototype Foamy Virus Protease-Reverse Transcriptase (PR-RT) 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.