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 that the receptor binding domain (RBD) of the spike of SARS-CoV-2 can bind HS in a length- and sequence-dependent manner. Hexa- and octa-saccharides composed of IdoA2S-GlcNS6S repeating units were identified as optimal ligands. Surface plasma resonance (SPR) showed the SARS-CoV-2 spike protein binds with much higher affinity to heparin (KD = 55 nM) compared to the RBD (KD = 1 uM) alone. We also found that heparin does not interfere in angiotensin-converting enzyme 2 (ACE2) binding or proteolytic processing of the spike. Our data supports a model in which HS functions as the point of initial attachment for SARS-CoV-2 infection. Tissue staining studies using biologically relevant tissues indicate that heparan sulfate proteoglycan (HSPG) is a critical attachment factor for the virus. Collectively, our results highlight the potential of using HS oligosaccharides as a therapeutic agent by inhibiting SARS-CoV-2 binding to target cells.

中文翻译：

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SARS-CoV-2 刺突蛋白以长度和序列依赖性方式结合硫酸乙酰肝素。

我们的数据支持一个模型，其中 HS 作为 SARS-CoV-2 感染的初始附着点。使用生物学相关组织的组织染色研究表明硫酸乙酰肝素蛋白聚糖 (HSPG) 是病毒的关键附着因子。总的来说，我们的结果突出了通过抑制 SARS-CoV-2 与靶细胞结合来使用 HS 寡糖作为治疗剂的潜力。