Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2

Lili Wu; Qian Chen; Kefang Liu; Jia Wang; Pengcheng Han; Yanfang Zhang; Yu Hu; Yumin Meng; Xiaoqian Pan; Chengpeng Qiao; Siyu Tian; Pei Du; Hao Song; Weifeng Shi; Jianxun Qi; Hong-Wei Wang; Jinghua Yan; George Fu Gao; Qihui Wang

doi:10.1038/s41421-020-00210-9

Broad host range of SARS-CoV-2 and the molecular basis for SARS-CoV-2 binding to cat ACE2

Cell Discov. 2020 Sep 29:6:68. doi: 10.1038/s41421-020-00210-9. eCollection 2020.

Authors

Lili Wu^#^{1

2}, Qian Chen^#^{1

3}, Kefang Liu^#^{2

4

5}, Jia Wang^#⁶, Pengcheng Han⁷, Yanfang Zhang^{4

8}, Yu Hu^{4

9}, Yumin Meng⁴, Xiaoqian Pan^{2

4}, Chengpeng Qiao¹, Siyu Tian^{1

2}, Pei Du¹, Hao Song¹⁰, Weifeng Shi¹¹, Jianxun Qi^{4

12}, Hong-Wei Wang⁶, Jinghua Yan^{1

12}, George Fu Gao⁴, Qihui Wang^{1

3

12}

Affiliations

¹ CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101 China.
² University of Chinese Academy of Sciences, Beijing, 100049 China.
³ Institute of Physical Science and Information, Anhui University, Hefei, Anhui 230039 China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101 China.
⁵ Faculty of Health Sciences, University of Macau, Macau, SAR China.
⁶ Ministry of Education Key Laboratory of Protein Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center of Biological Structures, School of Life Sciences, Tsinghua University, Beijing, 100084 China.
⁷ Department of biomedical engineering, Emory University, Atlanta, GA 10033 USA.
⁸ Laboratory of Protein Engineering and Vaccines,Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308 China.
⁹ School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 China.
¹⁰ Research Network of Immunity and Health (RNIH), Beijing Institute of Life Science, Chinese Academy of Sciences, Beijing, 100101 China.
¹¹ Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong 27100 China.
¹² Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049 China.

^# Contributed equally.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the recent pandemic COVID-19, is reported to have originated from bats, with its intermediate host unknown to date. Here, we screened 26 animal counterparts of the human ACE2 (hACE2), the receptor for SARS-CoV-2 and SARS-CoV, and found that the ACE2s from various species, including pets, domestic animals and multiple wild animals, could bind to SARS-CoV-2 receptor binding domain (RBD) and facilitate the transduction of SARS-CoV-2 pseudovirus. Comparing to SARS-CoV-2, SARS-CoV seems to have a slightly wider range in choosing its receptor. We further resolved the cryo-electron microscopy (cryo-EM) structure of the cat ACE2 (cACE2) in complex with the SARS-CoV-2 RBD at a resolution of 3 Å, revealing similar binding mode as hACE2 to the SARS-CoV-2 RBD. These results shed light on pursuing the intermediate host of SARS-CoV-2 and highlight the necessity of monitoring susceptible hosts to prevent further outbreaks.

Keywords: Cryoelectron microscopy; Molecular biology.

Abstract

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