Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates.
Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates.
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DOI：
10.1073/pnas.2010146117
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发表时间：
2020-09-08
影响因子：
11.1
通讯作者：
Lewin, Harris A
中科院分区：
文献类型：
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作者：
Damas, Joana;Hughes, Graham M;Lewin, Harris A
新型冠状病毒 SARS-CoV-2 是 2019 年冠状病毒病 (COVID-19) 的病因。 SARS-CoV-2 的主要受体血管紧张素 I 转换酶 2 (ACE2) 目前正在接受广泛的审查，以了解不同物种的传播途径和敏感性。在这里，我们利用了 410 种脊椎动物（包括 252 种哺乳动物）的独特数据集来研究 ACE2 的跨物种保护及其作为 SARS-CoV-2 受体发挥作用的可能性。我们根据对受体和病毒之间的结合很重要的 25 个氨基酸的保守特性，设计了一个五类排名评分，将所有物种从非常高到非常低进行分类。只有哺乳动物属于中到非常高的类别，只有卡他灵长类动物属于非常高的类别，这表明它们感染 SARS-CoV-2 的风险很高。我们采用蛋白质结构分析来定性评估可变残基的氨基酸变化是否可能破坏 ACE2/SARS-CoV-2 结合，并发现预测的不利变化数量与结合评分显着相关。将这种分析扩展到人口数据，我们发现只有罕见的（
The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low. Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (