Predicting susceptibility to SARS-CoV-2 infection based on structural differences in ACE2 across species.
Predicting susceptibility to SARS-CoV-2 infection based on structural differences in ACE2 across species.
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DOI：
10.1096/fj.202001808r
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Madhur MS
中科院分区：
文献类型：
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作者：
Alexander MR;Schoeder CT;Brown JA;Smart CD;Moth C;Wikswo JP;Capra JA;Meiler J;Chen W;Madhur MS
严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）是2019年冠状病毒病（COVID-19）全球大流行的原因。SARS-CoV-2是一种人畜共患疾病，但对物种易感性的变化知之甚少，这些变化可以识别潜在的宿主物种，动物模型以及对宠物，野生动物和牲畜的风险。某些物种，如家猫和老虎，易受SARS-CoV-2感染，而其他物种，如小鼠和鸡则不会。大多数动物物种，包括与人类密切接触的动物，都有未知的易感性。因此，迫切需要预测动物物种感染风险的方法。SARS-CoV-2刺突蛋白与血管紧张素转换酶2（ACE 2）的结合对于病毒进入细胞和感染至关重要。在这里，我们将易感性的物种差异与多个深入的结构分析相结合，以确定区分易感物种和耐药物种的关键ACE 2氨基酸位置，包括30，83，90，322和354。利用这些残留物在物种间的差异，我们开发了一种易感性评分，预测包括马和骆驼在内的多个物种感染SARS-CoV-2的风险升高。我们还证明，与其他动物相比，SARS-CoV-2几乎是结合人类ACE 2的最佳选择，这可能是该病毒在人类中高度传染性传播的基础。总之，我们的研究结果定义了潜在的ACE 2和SARS-CoV-2残留物，用于治疗靶向和识别动物物种，重点研究和保护环境和公共卫生措施。
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the cause of the global pandemic of coronavirus disease‐2019 (COVID‐19). SARS‐CoV‐2 is a zoonotic disease, but little is known about variations in species susceptibility that could identify potential reservoir species, animal models, and the risk to pets, wildlife, and livestock. Certain species, such as domestic cats and tigers, are susceptible to SARS‐CoV‐2 infection, while other species such as mice and chickens are not. Most animal species, including those in close contact with humans, have unknown susceptibility. Hence, methods to predict the infection risk of animal species are urgently needed. SARS‐CoV‐2 spike protein binding to angiotensin‐converting enzyme 2 (ACE2) is critical for viral cell entry and infection. Here we integrate species differences in susceptibility with multiple in‐depth structural analyses to identify key ACE2 amino acid positions including 30, 83, 90, 322, and 354 that distinguish susceptible from resistant species. Using differences in these residues across species, we developed a susceptibility score that predicts an elevated risk of SARS‐CoV‐2 infection for multiple species including horses and camels. We also demonstrate that SARS‐CoV‐2 is nearly optimal for binding ACE2 of humans compared to other animals, which may underlie the highly contagious transmissibility of this virus among humans. Taken together, our findings define potential ACE2 and SARS‐CoV‐2 residues for therapeutic targeting and identification of animal species on which to focus research and protection measures for environmental and public health.