The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity
The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity
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DOI：
10.1016/j.cell.2020.07.012
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发表时间：
2020-09-03
期刊：
影响因子：
64.5
通讯作者：
Wang, Youchun
中科院分区：
文献类型：
--
作者：
Li, Qianqian;Wu, Jiajing;Wang, Youchun
SARS-CoV-2 的刺突蛋白已经发生突变并且高度糖基化。研究这些突变的生物学意义至关重要。在这里，我们研究了 80 个变体和 26 个糖基化位点修饰对一组中和抗体和恢复期患者血清的感染性和反应性。 D614G 以及同时含有 D614G 和另一种氨基酸变化的几种变体具有明显更强的传染性。大多数受体结合域发生氨基酸变化的变体感染性较低，但包括 A475V、L452R、V483A 和 F490L 在内的变体对某些中和抗体产生抗性。此外，大多数糖基化缺失的感染性较低，而 N331 和 N343 糖基化的缺失则大大降低了感染性，揭示了糖基化对病毒感染性的重要性。有趣的是，N234Q 对中和抗体具有明显的抵抗力，而 N165Q 变得更加敏感。这些发现可能对疫苗和治疗性抗体的开发有价值。
The spike protein of SARS-CoV-2 has been undergoing mutations and is highly glycosylated. It is critically important to investigate the biological significance of these mutations. Here, we investigated 80 variants and 26 glycosylation site modifications for the infectivity and reactivity to a panel of neutralizing antibodies and sera from convalescent patients. D614G, along with several variants containing both D614G and another amino acid change, were significantly more infectious. Most variants with amino acid change at receptor binding domain were less infectious, but variants including A475V, L452R, V483A, and F490L became resistant to some neutralizing antibodies. Moreover, the majority of glycosylation deletions were less infectious, whereas deletion of both N331 and N343 glycosylation drastically reduced infectivity, revealing the importance of glycosylation for viral infectivity. Interestingly, N234Q was markedly resistant to neutralizing antibodies, whereas N165Q became more sensitive. These findings could be of value in the development of vaccine and therapeutic antibodies.