Cross-species recognition and molecular basis of SARS-CoV-2 and SARS-CoV binding to ACE2s of marine animals

Shihua Li; Ruirui Yang; Di Zhang; Pu Han; Zepeng Xu; Qian Chen; Runchu Zhao; Xin Zhao; Xiao Qu; Anqi Zheng; Liang Wang; Linjie Li; Yu Hu; Rong Zhang; Chao Su; Sheng Niu; Yanfang Zhang; Jianxun Qi; Kefang Liu; Qihui Wang; George F Gao

doi:10.1093/nsr/nwac122

Cross-species recognition and molecular basis of SARS-CoV-2 and SARS-CoV binding to ACE2s of marine animals

Natl Sci Rev. 2022 Jun 23;9(9):nwac122. doi: 10.1093/nsr/nwac122. eCollection 2022 Sep.

Authors

Shihua Li¹, Ruirui Yang^{1

2}, Di Zhang^{1

3}, Pu Han¹, Zepeng Xu^{1

3}, Qian Chen^{1

4}, Runchu Zhao^{1

4}, Xin Zhao^{1

5}, Xiao Qu¹, Anqi Zheng¹, Liang Wang^{1

5}, Linjie Li^{1

6}, Yu Hu^{1

7}, Rong Zhang^{1

8}, Chao Su¹, Sheng Niu^{1

2}, Yanfang Zhang¹, Jianxun Qi^{1

6}, Kefang Liu¹, Qihui Wang^{1

2

6}, George F Gao^{1

2

6}

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing100101, China.
² College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong030801, China.
³ Faculty of Health Sciences, University of Macau, Macau, China.
⁴ Institute of Physical Science and Information, Anhui University, Hefei230039, China.
⁵ Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing100101, China.
⁶ Savaid Medical School, University of Chinese Academy of Sciences, Beijing100049, China.
⁷ School of Life Sciences, University of Science and Technology of China, Hefei230026, China.
⁸ State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning530004, China.

Abstract

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.

Keywords: SARS-CoV-2; cross-species recognition; cryo-EM structure; marine animals.