SARS-CoV-2 variant evades antibodies whilst maintaining fitness.
SARS-CoV-2 variant evades antibodies whilst maintaining fitness.
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SARS-CoV-2变体在保持健康的同时逃避抗体。
DOI：
10.1038/s41577-021-00510-5
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Flemming A
中科院分区：
文献类型：
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作者：
Flemming A
SARS-CoV-2 N439 K突变位于刺突蛋白的受体结合基序（RBM）中，已多次独立出现，是第一个显著传播的RBM变体。Thomson等人现在证明，作为中和抗体的主要靶标的RBM在结构上是可塑的，并且N439 K突变赋予对人ACE 2（病毒进入受体）的约两倍增强的结合亲和力，而没有复制适应性的损失，并且具有与祖先病毒感染相似的临床结果。他们还表明，该突变赋予了对几种中和单克隆抗体的抗性，并允许来自感染后恢复的个体的一些多克隆血清的免疫逃逸。RBM可以很容易地突变而不丧失适应性的事实表明，尽管病毒的突变速度很慢，但潜在的免疫逃避变体将继续出现-这确实是自本研究完成以来观察到的。
The SARS-CoV-2 N439K mutation, located in the receptorbinding motif (RBM) of the spike protein, has emerged multiple times independently and was the first RBM variant to spread significantly. Thomson et al. now demonstrate that the RBM, which is the primary target for neutralizing antibodies, is structurally plastic and that the N439K mutation confers an approximately twofold enhanced binding affinity for human ACE2 (the viral entry receptor), without a loss in replication fitness and with similar clinical outcomes to infection with the ancestral virus. They also show that the mutation confers resistance to several neutralizing monoclonal antibodies and allows for immune escape from some polyclonal sera derived from individuals who recovered from infection. The fact that the RBM can readily mutate without loss of fitness indicates that despite the slow mutation rate of the virus, potentially immune-evading variants will continue to emerge—which has indeed been observed since the completion of this study.