PT  - JOURNAL ARTICLE
AU  - Lin Liu
AU  - Pradeep Chopra
AU  - Xiuru Li
AU  - Margreet A. Wolfert
AU  - S. Mark Tompkins
AU  - Geert-Jan Boons
TI  - SARS-CoV-2 spike protein binds heparan sulfate in a length- and sequence-dependent manner
AID  - 10.1101/2020.05.10.087288
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.10.087288
4099  - http://biorxiv.org/content/early/2020/05/10/2020.05.10.087288.short
4100  - http://biorxiv.org/content/early/2020/05/10/2020.05.10.087288.full
AB  - 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 µM) 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.Competing Interest StatementThe authors have declared no competing interest.