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SARS-CoV-2 spike protein binds heparan sulfate in a length- and sequence-dependent manner (preprint)
biorxiv; 2020.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2020.05.10.087288
ABSTRACT
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. Microarray binding experiments using an extensive heparan sulfate (HS) oligosaccharide library showed the spike of SARS-CoV-2 can bind HS in a length- and sequence-dependent manner. Hexa- and octasaccharides composed of IdoA2S-GlcNS6S repeating units were identified as optimal ligands. Surface plasma resonance (SPR) showed the SARS-CoV-2 spike protein binds with higher affinity to heparin (KD 55 nM) compared to the receptor binding domain (RBD, KD 1 {micro}M) alone. An octasaccharide composed of IdoA2S-GlcNS6S could inhibit spike-heparin interaction with an IC50 of 38 nM. Our data supports a model in which the RBD of the spike of SARS-CoV-2 confers sequence specificity for HS expressed by target cells whereas an additional HS binding site in the S1/S2 proteolytic cleavage site enhances the avidity of binding. Collectively, our results highlight the potential of using HS oligosaccharides as a therapeutic agent by inhibiting SARS-CoV-2 binding to target cells.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Main subject:
Severe Acute Respiratory Syndrome
Language:
English
Year:
2020
Document Type:
Preprint
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