Background: Several new variants of SARS-CoV-2 have emerged since fall 2020 which have multiple mutations in the receptor binding domain (RBD) of the spike protein. Objective: We aimed to assess how mutations in the SARS-CoV-2 RBD affect receptor affinity to angiotensin-converting enzyme 2 (ACE2) and neutralization by anti-RBD serum antibodies. Methods: We produced a SARS-CoV-2 RBD mutant (RBDmut) with key mutations (E484K, K417N, N501Y) from the newly emerged Brazilian variant. Using Biolayer Interferometry, we analyzed the binding of this mutant to ACE2, and the susceptibility to neutralization by sera from vaccinated mice and COVID-19 convalescent patients. Results: Kinetic profiles showed increased RBDmut - ACE2 affinity compared to RBDwt, and binding of vaccine-elicited or convalescent sera was significantly reduced. Likewise, both sera types showed significantly reduced ability to block RBDmut - ACE2 binding indicating that antibodies induced by RBDwt have reduced capability to neutralize mutant virus. Conclusion: Our physiochemical data show enhanced infectivity and reduced neutralization by polyclonal antibodies of the Brazilian variant of SARS-CoV-2.

中文翻译：

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对ACE2具有更高亲和力的SARS-CoV-2变体显示降低的血清中和敏感性

背景：自2020年秋季以来，出现了SARS-CoV-2的几种新变体，它们在刺突蛋白的受体结合域（RBD）中具有多个突变。目的：我们旨在评估SARS-CoV-2 RBD中的突变如何影响受体对血管紧张素转化酶2（ACE2）的亲和力以及抗RBD血清抗体的中和作用。方法：我们从新出现的巴西变种中产生了具有关键突变（E484K，K417N，N501Y）的SARS-CoV-2 RBD突变体（RBDmut）。使用生物层干涉术，我们分析了该突变体与ACE2的结合，以及接种疫苗的小鼠和COVID-19恢复期患者血清对中和的敏感性。结果：动力学概况显示，与RBDwt相比，RBDmut-ACE2亲和力增加，并且疫苗诱导或恢复期血清的结合显着降低。同样地，两种血清均显示出显着降低的阻断RBDmut-ACE2结合的能力，这表明RBDwt诱导的抗体中和突变病毒的能力降低。结论：我们的理化数据显示，SARS-CoV-2巴西变异体的多克隆抗体可增强感染性，并减少中和作用。