Li Shihua, Yang Ruirui, Zhang Di, Han Pu, Xu Zepeng, Chen Qian, Zhao Runchu, Zhao Xin, Qu Xiao, Zheng Anqi, Wang Liang, Li Linjie, Hu Yu, Zhang Rong, Su Chao, Niu Sheng, Zhang Yanfang, Qi Jianxun, Liu Kefang, Wang Qihui, Gao George F
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing100101, China.
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong030801, China.
Natl Sci Rev. 2022 Jun 23;9(9):nwac122. doi: 10.1093/nsr/nwac122. eCollection 2022 Sep.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has an extremely broad host range that includes hippopotami, which are phylogenetically closely related to whales. The cellular ACE2 receptor is one of the key determinants of the host range. Here, we found that ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of both SARS-CoV and SARS-CoV-2 and facilitate the transduction of SARS-CoV and SARS-CoV-2 pseudoviruses into ACE2-expressing cells. We further resolved the cryo-electron microscopy complex structures of the minke whale ACE2 and sea lion ACE2, respectively, bound to the RBDs, revealing that they have similar binding modes to human ACE2 when it comes to the SARS-CoV-2 RBD and SARS-CoV RBD. Our results indicate that marine mammals could potentially be new victims or virus carriers of SARS-CoV-2, which deserves further careful investigation and study. It will provide an early warning for the prospective monitoring of marine mammals.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）具有极其广泛的宿主范围，其中包括与鲸鱼在系统发育上密切相关的河马。细胞ACE2受体是宿主范围的关键决定因素之一。在此，我们发现几种海洋哺乳动物和河马的ACE2能够有效地结合SARS-CoV和SARS-CoV-2的受体结合域（RBD），并促进SARS-CoV和SARS-CoV-2假病毒转导至表达ACE2的细胞中。我们进一步分别解析了小须鲸ACE2和海狮ACE2与RBD结合的冷冻电镜复合物结构，结果显示，在与SARS-CoV-2 RBD和SARS-CoV RBD结合时，它们与人类ACE2具有相似的结合模式。我们的结果表明，海洋哺乳动物有可能成为SARS-CoV-2的新受害者或病毒携带者，这值得进一步仔细调查和研究。这将为对海洋哺乳动物的前瞻性监测提供早期预警。
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