The B.1.1.7 variant of SARS-CoV-2 first detected in the UK harbors amino-acid substitutions and deletions in the spike protein that potentially enhance host angiotensin conversion enzyme 2 (ACE2) receptor binding and viral immune evasion. Here we report cryo-EM structures of the spike protein of B.1.1.7 in the apo and ACE2-bound forms. The apo form showed one or two receptor-binding domains (RBDs) in the open conformation, without populating the fully closed state. All three RBDs were engaged in ACE2 binding. The B.1.1.7-specific A570D mutation introduces a molecular switch that could modulate the opening and closing of the RBD. The N501Y mutation introduces a π–π interaction that enhances RBD binding to ACE2 and abolishes binding of a potent neutralizing antibody (nAb). Cryo-EM also revealed how a cocktail of two nAbs simultaneously bind to all three RBDs, and demonstrated the potency of the nAb cocktail to neutralize different SARS-CoV-2 pseudovirus strains, including B.1.1.7.

在英国首次发现的 SARS-CoV-2 的 B.1.1.7 变体在刺突蛋白中含有氨基酸取代和缺失，可能增强宿主血管紧张素转化酶 2 (ACE2) 受体的结合和病毒免疫逃避。在这里，我们报告了 Apo 和 ACE2 结合形式的 B.1.1.7 刺突蛋白的冷冻电镜结构。apo 形式在开放构象中显示出一个或两个受体结合域 (RBD)，而没有填充完全闭合状态。所有三个 RBD 都参与了 ACE2 结合。B.1.1.7 特异性 A570D 突变引入了一个分子开关，可以调节 RBD 的打开和关闭。N501Y 突变引入了π – π增强 RBD 与 ACE2 的结合并消除强效中和抗体 (nAb) 的结合。Cryo-EM 还揭示了两种 nAb 的混合物如何同时与所有三种 RBD 结合，并证明了 nAb 混合物中和不同 SARS-CoV-2 假病毒株（包括 B.1.1.7）的效力。