Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a new virus that has higher contagious capacity than any other previous human coronaviruses (HCoVs) and causes the current coronavirus disease 2019 pandemic. Sialic acids are a group of nine-carbon acidic α-keto sugars, usually located at the end of glycans of cell surface glycoconjugates and serve as attachment sites for previous HCoVs. It is therefore speculated that sialic acids on the host cell surface could serve as co-receptors or attachment factors for SARS-CoV-2 cell entry as well. Recent in silico modeling, molecular modeling predictions and microscopy studies indicate potential sialic acid binding by SARS-CoV-2 upon cell entry. In particular, a flat sialic acid-binding domain was proposed at the N-terminal domain of the spike protein, which may lead to the initial contact and interaction of the virus on the epithelium followed by higher affinity binding to angiotensin-converting enzyme 2 (ACE2) receptor, likely a two-step attachment fashion. However, recent in vitro and ex vivo studies of sialic acids on ACE2 receptor confirmed an opposite role for SARS-CoV-2 binding. In particular, neuraminidase treatment of epithelial cells and ACE2-expressing 293T cells increased SARS-CoV-2 binding. Furthermore, the ACE2 glycosylation inhibition studies indicate that sialic acids on ACE2 receptor prevent ACE2-spike protein interaction. On the other hand, a most recent study indicates that gangliosides could serve as ligands for receptor-binding domain of SARS-CoV-2 spike protein. This mini-review discusses what has been predicted and known so far about the role of sialic acid for SARS-CoV-2 infection and future research perspective.

中文翻译：

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细胞表面唾液酸在 SARS-CoV-2 感染中的作用。


严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 是一种新病毒，比之前任何其他人类冠状病毒 (HCoV) 具有更高的传染能力，并导致当前的 2019 年冠状病毒病大流行。唾液酸是一组九碳酸性α-酮糖，通常位于细胞表面糖复合物的聚糖末端，并作为先前HCoV的附着位点。因此推测宿主细胞表面的唾液酸也可以作为 SARS-CoV-2 进入细胞的辅助受体或附着因子。最近的计算机模型、分子模型预测和显微镜研究表明，SARS-CoV-2 在进入细胞后可能与唾液酸结合。特别是，在刺突蛋白的 N 端结构域提出了一个平坦的唾液酸结合结构域，这可能导致病毒在上皮上的初始接触和相互作用，然后与血管紧张素转换酶 2 具有更高的亲和力结合（ ACE2) 受体，可能是一种两步附着方式。然而，最近对 ACE2 受体上唾液酸的体外和离体研究证实了 SARS-CoV-2 结合的相反作用。特别是，神经氨酸酶处理上皮细胞和表达 ACE2 的 293T 细胞增加了 SARS-CoV-2 的结合。此外，ACE2 糖基化抑制研究表明 ACE2 受体上的唾液酸可防止 ACE2 与刺突蛋白相互作用。另一方面，最近的一项研究表明，神经节苷脂可以作为 SARS-CoV-2 刺突蛋白受体结合域的配体。这篇小评论讨论了迄今为止关于唾液酸在 SARS-CoV-2 感染中的作用的预测和已知信息以及未来的研究前景。