CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.
Nat Commun. 2022 Jun 21;13(1):3547. doi: 10.1038/s41467-022-31276-6.
The origin and host range of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), are important scientific questions as they might provide insight into understanding of the potential future spillover to infect humans. Here, we tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin coronavirus (CoV) RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019. We also determined the crystal structures of eqACE2/RaTG13-RBD, eqACE2/SARS-CoV-2 PT-RBD and eqACE2/Omicron BA.1-RBD. We identified S494 of SARS-COV-2 PT-RBD as an important residue in the eqACE2/SARS-COV-2 PT-RBD interaction and found that N501Y, the commonly recognized enhancing mutation, attenuated the binding affinity with eqACE2. Our work demonstrates that horses are potential targets for SARS-CoV-2 and highlights the importance of continuous surveillance on SARS-CoV-2 and related CoVs to prevent spillover events.
SARS-CoV-2 的起源和宿主范围是引起 2019 年冠状病毒病（COVID-19）的病原体，这是一个重要的科学问题，因为它可能有助于理解潜在的未来溢出感染人类的风险。在这里，我们测试了马血管紧张素转换酶 2（eqACE2）与 SARS-CoV、SARS-CoV-2 原型（PT）和关注变体（VOCs）的受体结合域（RBD）以及它们的近亲蝙蝠起源冠状病毒（CoV）RaTG13 和穿山甲起源的 CoVs GX/P2V/2017 和 GD/1/2019 之间的结合。我们还确定了 eqACE2/RaTG13-RBD、eqACE2/SARS-CoV-2 PT-RBD 和 eqACE2/Omicron BA.1-RBD 的晶体结构。我们确定了 SARS-CoV-2 PT-RBD 的 S494 是 eqACE2/SARS-CoV-2 PT-RBD 相互作用中的一个重要残基，并且发现普遍认为增强突变的 N501Y 降低了与 eqACE2 的结合亲和力。我们的工作表明马是 SARS-CoV-2 的潜在靶标，并强调了对 SARS-CoV-2 和相关 CoVs 进行持续监测以防止溢出事件的重要性。
