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.

中文翻译：

---

基于物种间 ACE2 的结构差异预测对 SARS-CoV-2 感染的易感性

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 是导致 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，但对于可以识别潜在宿主物种、动物模型以及对宠物、野生动物和牲畜的风险的物种易感性变化知之甚少。某些物种，如家猫和老虎，容易感染 SARS-CoV-2，而其他物种，如老鼠和鸡则不然。大多数动物物种，包括与人类密切接触的动物，都具有未知的易感性。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 (ACE2) 的结合对于病毒细胞进入和感染至关重要。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，以确定关键的 ACE2 氨基酸位置，包括 30、83、90、322 和 354 位，以区分易感性和抗性物种。利用这些残留物在物种间的差异，我们开发了一个敏感性评分，可以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 在结合人类 ACE2 方面几乎是最佳的，这可能是这种病毒在人类中具有高度传染性的基础。总之，我们的研究结果确定了潜在的 ACE2 和 SARS-CoV-2 残留物，用于治疗靶向和鉴定动物物种，重点研究和保护环境和公共卫生措施。