The current pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outbreaks of new variants highlight the need for preventive treatments. Here, we identified heparan sulfate proteoglycans as attachment receptors for SARS-CoV-2. Notably, neutralizing antibodies against SARS-CoV-2 isolated from COVID-19 patients interfered with SARS-CoV-2 binding to heparan sulfate proteoglycans, which might be an additional mechanism of antibodies to neutralize infection. SARS-CoV-2 binding to and infection of epithelial cells was blocked by low molecular weight heparins (LMWH). Although dendritic cells (DCs) and mucosal Langerhans cells (LCs) were not infected by SARS-CoV-2, both DC subsets efficiently captured SARS-CoV-2 via heparan sulfate proteoglycans and transmitted the virus to ACE2-positive cells. Notably, human primary nasal cells were infected by SARS-CoV-2, and infection was blocked by pre-treatment with LMWH. These data strongly suggest that heparan sulfate proteoglycans are important attachment receptors facilitating infection and transmission, and support the use of LMWH as prophylaxis against SARS-CoV-2 infection.

中文翻译：

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SARS-CoV-2的感染和传播依赖于硫酸乙酰肝素蛋白聚糖

当前由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的大流行以及新变种的爆发凸显了预防性治疗的必要性。在这里，我们确定了硫酸乙酰肝素蛋白聚糖作为 SARS-CoV-2 的附着受体。值得注意的是，从 COVID-19 患者中分离出的针对 SARS-CoV-2 的中和抗体会干扰 SARS-CoV-2 与硫酸乙酰肝素蛋白聚糖的结合，这可能是抗体中和感染的另一种机制。低分子量肝素 (LMWH) 阻断了 SARS-CoV-2 与上皮细胞的结合和感染。尽管树突状细胞 (DC) 和粘膜朗格汉斯细胞 (LC) 没有被 SARS-CoV-2 感染，但这两个 DC 亚群都通过硫酸乙酰肝素蛋白聚糖有效捕获 SARS-CoV-2，并将病毒传播给 ACE2 阳性细胞。值得注意的是，人类原代鼻细胞被 SARS-CoV-2 感染，并且通过 LMWH 预处理来阻止感染。这些数据强烈表明，硫酸乙酰肝素蛋白多糖是促进感染和传播的重要附着受体，并支持使用 LMWH 来预防 SARS-CoV-2 感染。