The emergence of SARS‐CoV‐2 has resulted in nearly 1,280,000 infections and 73,000 deaths globally so far. This novel virus acquired the ability to infect human cells using the SARS‐CoV cell receptor hACE2. Because of this, it is essential to improve our understanding of the evolutionary dynamics surrounding the SARS‐CoV‐2 hACE2 interaction. One way theory predicts selection pressures should shape viral evolution is to enhance binding with host cells. We first assessed evolutionary dynamics in select betacoronavirus spike protein genes to predict whether these genomic regions are under directional or purifying selection between divergent viral lineages, at various scales of relatedness. With this analysis, we determine a region inside the receptor‐binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor ACE2. Next, to gain further insights into factors associated with recognition of the human host receptor, we performed modeling studies of five different betacoronaviruses and their potential binding to hACE2. Modeling results indicate that interfering with the salt bridges at hot spot 353 could be an effective strategy for inhibiting binding, and hence for the prevention of SARS‐CoV‐2 infections. We also propose that a glycine residue at the receptor‐binding domain of the spike glycoprotein can have a critical role in permitting bat SARS‐related coronaviruses to infect human cells.

中文翻译：

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SARS-CoV-2，从与人类 ACE2 相互作用的进化角度揭示了复杂稳定性所必需的未被发现的氨基酸。

迄今为止，SARS-CoV-2 的出现已导致全球近 1,280,000 例感染和 73,000 例死亡。这种新型病毒获得了利用 SARS-CoV 细胞受体 hACE2 感染人类细胞的能力。因此，有必要提高我们对围绕 SARS-CoV-2 hACE2 相互作用的进化动力学的理解。理论预测选择压力影响病毒进化的一种方式是增强与宿主细胞的结合。我们首先评估了选定的β冠状病毒刺突蛋白基因的进化动态，以预测这些基因组区域是否处于不同病毒谱系之间以不同相关性尺度进行定向或纯化选择。通过此分析，我们确定了受体结合域内的一个区域，其正选择下的推定位点散布在高度保守的位点中，这些位点与病毒刺突蛋白的结构稳定性及其与人类受体 ACE2 的结合有关。接下来，为了进一步了解与人类宿主受体识别相关的因素，我们对五种不同的 β 冠状病毒及其与 hACE2 的潜在结合进行了建模研究。建模结果表明，干扰热点 353 处的盐桥可能是抑制结合的有效策略，从而预防 SARS-CoV-2 感染。我们还提出，刺突糖蛋白受体结合域的甘氨酸残基在允许蝙蝠 SARS 相关冠状病毒感染人类细胞方面发挥着关键作用。