SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability
SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability
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DOI：
10.1111/eva.12980
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发表时间：
2020-05-07
影响因子：
4.1
通讯作者：
Perez-Castillo, Yunierkis
中科院分区：
文献类型：
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作者：
Armijos-Jaramillo, Vinicio;Yeager, Justin;Perez-Castillo, Yunierkis
到目前为止，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使用SARS-CoV细胞受体hACE 2感染人类细胞的能力。因此，有必要提高我们对SARS-CoV-2 hACE 2相互作用的进化动力学的理解。理论预测，选择压力会影响病毒进化的一种方式是增强与宿主细胞的结合。我们首先评估了选择β冠状病毒刺突蛋白基因的进化动力学，以预测这些基因组区域是否在不同的病毒谱系之间，在各种相关性尺度上进行定向或纯化选择。通过这种分析，我们确定了一个区域内的受体结合结构域与假定的网站之间的高度保守的网站，这是有牵连的病毒刺突蛋白的结构稳定性和它的工会与人类受体ACE 2的正选择散布。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hACE 2的潜在结合进行了建模研究。模拟结果表明，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，在刺突糖蛋白的受体结合结构域的甘氨酸残基可以有一个关键的作用，允许蝙蝠SARS相关的冠状病毒感染人类细胞。
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.