tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2023 Sep 19;120(38):e2301518120.
doi: 10.1073/pnas.2301518120. Epub 2023 Sep 11. Targeting spike glycans to inhibit SARS-CoV2 viral entry
Alex J Guseman[SUP] 1 [/SUP], Linda J Rennick[SUP] 2 [/SUP], Sham Nambulli[SUP] 2 [/SUP], Chandra N Roy[SUP] 2 [/SUP], David R Martinez[SUP] 3 [/SUP], Darian T Yang[SUP] 1 [/SUP], Fatema Bhinderwala[SUP] 1 [/SUP], Sandra Vergara[SUP] 1 [/SUP], Alexandra Schaefer[SUP] 3 [/SUP], Ralph S Baric[SUP] 3 [/SUP], Zandrea Ambrose[SUP] 2 [/SUP], W Paul Duprex[SUP] 2 [/SUP], Angela M Gronenborn[SUP] 1 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; glycan shield; lectins.
. 2023 Sep 19;120(38):e2301518120.
doi: 10.1073/pnas.2301518120. Epub 2023 Sep 11. Targeting spike glycans to inhibit SARS-CoV2 viral entry
Alex J Guseman[SUP] 1 [/SUP], Linda J Rennick[SUP] 2 [/SUP], Sham Nambulli[SUP] 2 [/SUP], Chandra N Roy[SUP] 2 [/SUP], David R Martinez[SUP] 3 [/SUP], Darian T Yang[SUP] 1 [/SUP], Fatema Bhinderwala[SUP] 1 [/SUP], Sandra Vergara[SUP] 1 [/SUP], Alexandra Schaefer[SUP] 3 [/SUP], Ralph S Baric[SUP] 3 [/SUP], Zandrea Ambrose[SUP] 2 [/SUP], W Paul Duprex[SUP] 2 [/SUP], Angela M Gronenborn[SUP] 1 [/SUP]
Affiliations
- PMID: 37695910
- DOI: 10.1073/pnas.2301518120
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.
Keywords: SARS-CoV-2; glycan shield; lectins.