The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal respiratory illness in humans, and no vaccines or specific treatments are available. Infections are initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides and dipeptidyl-peptidase 4 (the attachment and entry receptors, respectively). To understand MERS-CoV engagement of sialylated receptors, we determined the cryo-EM structures of S in complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-LewisX, α2,3-sialyl-N-acetyl-lactosamine and α2,6-sialyl-N-acetyl-lactosamine at 2.7-3.0 Å resolution. We show that recognition occurs via a conserved groove that is essential for MERS-CoV S-mediated attachment to sialosides and entry into human airway epithelial cells. Our data illuminate MERS-CoV S sialoside specificity and suggest that selectivity for α2,3-linked over α2,6-linked receptors results from enhanced interactions with the former class of oligosaccharides. This study provides a structural framework explaining MERS-CoV attachment to sialoside receptors and identifies a site of potential vulnerability to inhibitors of viral entry.

中文翻译：

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MERS-CoV 刺突糖蛋白与唾液苷附着受体复合的结构。

中东呼吸综合征冠状病毒 (MERS-CoV) 会导致人类出现严重且通常是致命的呼吸道疾病，目前尚无疫苗或特定治疗方法。感染是通过 MERS-CoV 刺突 (S) 糖蛋白与唾液酸苷和二肽基肽酶 4（分别为附着和进入受体）结合而引发的。为了了解 MERS-CoV 与唾液酸化受体的结合，我们确定了 S 与 5-N-乙酰神经氨酸、5-N-羟乙酰神经氨酸、唾液酸-LewisX、α2,3-唾液酸-N-复合物的冷冻电镜结构乙酰-乳糖胺和 α2,6-唾液酸-N-乙酰-乳糖胺，分辨率为 2.7-3.0 Å。我们表明，识别是通过一个保守的凹槽发生的，该凹槽对于 MERS-CoV S 介导的唾液酸苷附着和进入人体气道上皮细胞至关重要。我们的数据阐明了 MERS-CoV S 唾液酸苷的特异性，并表明 α2,3 连接受体优于 α2,6 连接受体的选择性是由于与前一类寡糖的相互作用增强所致。该研究提供了一个结构框架，解释了 MERS-CoV 与唾液酸苷受体的结合，并确定了一个可能易受病毒进入抑制剂影响的位点。