SARS-CoV-2 entry in human cells is mediated by the interaction between the viral Spike protein and the human ACE2 receptor. This mechanism evolved from the ancestor bat coronavirus and is currently one of the main targets for antiviral strategies. However, there currently exist several Spike protein variants in the SARS-CoV-2 population as the result of mutations, and it is unclear if these variants may exert a specific effect on the affinity with ACE2 which, in turn, is also characterized by multiple alleles in the human population. In the current study, the GBPM analysis, originally developed for highlighting host-guest interaction features, has been applied to define the key amino acids responsible for the Spike/ACE2 molecular recognition, using four different crystallographic structures. Then, we intersected these structural results with the current mutational status, based on more than 295,000 sequenced cases, in the SARS-CoV-2 population. We identified several Spike mutations interacting with ACE2 and mutated in at least 20 distinct patients: S477N, N439K, N501Y, Y453F, E484K, K417N, S477I and G476S. Among these, mutation N501Y in particular is one of the events characterizing SARS-CoV-2 lineage B.1.1.7, which has recently risen in frequency in Europe. We also identified five ACE2 rare variants that may affect interaction with Spike and susceptibility to infection: S19P, E37K, M82I, E329G and G352V.

中文翻译：

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影响SARS CoV-2 Spike /人类ACE2复合体的循环变异体的结构遗传学

SARS-CoV-2进入人体细胞的过程是由病毒刺突蛋白和人类ACE2受体之间的相互作用介导的。该机制是从祖先蝙蝠冠状病毒进化而来，目前是抗病毒策略的主要目标之一。但是，由于突变，目前在SARS-CoV-2群体中存在几种Spike蛋白变体，目前尚不清楚这些变体是否会对与ACE2的亲和力产生特定影响，而ACE2的亲和力还具有多种特征。人群中的等位基因。在当前的研究中，最初用于突出宿主-客体相互作用特征的GBPM分析已使用四种不同的晶体学结构定义了负责Spike / ACE2分子识别的关键氨基酸。然后，我们基于SARS-CoV-2群体中超过295,000个测序病例，将这些结构结果与当前的突变状态相交。我们确定了几个与ACE2相互作用的Spike突变，并在至少20位不同的患者中发生了突变：S477N，N439K，N501Y，Y453F，E484K，K417N，S477I和G476S。其中，突变N501Y特别是SARS-CoV-2谱系B.1.1.7的特征之一，该谱系最近在欧洲的频率有所上升。我们还确定了五个ACE2罕见变体，它们可能影响与Spike的相互作用和感染的易感性：S19P，E37K，M82I，E329G和G352V。K417N，S477I和G476S。其中，突变N501Y特别是SARS-CoV-2谱系B.1.1.7的特征之一，该谱系最近在欧洲的频率有所上升。我们还确定了五个ACE2罕见变体，它们可能影响与Spike的相互作用和感染的易感性：S19P，E37K，M82I，E329G和G352V。K417N，S477I和G476S。其中，突变N501Y特别是SARS-CoV-2谱系B.1.1.7的特征之一，该谱系最近在欧洲的频率有所上升。我们还确定了五个ACE2罕见变体，它们可能影响与Spike的相互作用和感染的易感性：S19P，E37K，M82I，E329G和G352V。