OmniVira

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

Lili Wu1,2 Qian Chen1,3 Kefang Liu2,4,5 Jia Wang6 Pengcheng Han7 Yanfang Zhang4,8 Yu Hu4,9 Yumin Meng4 Xiaoqian Pan2,4 Chengpeng Qiao1 Siyu Tian1,2 Pei Du1 Hao Song10 Weifeng Shi11 Jianxun Qi4,12 Hong-Wei Wang6 Jinghua Yan1,12 George Fu Gao4 Qihui Wang1,3,12
Affiliations 12 institutions
  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.
PMID33020722 DOI10.1038/s41421-020-00210-9 Year2020 Journal Cell discovery Cell Discov Languageeng Statusepublish

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.

Supporting text Virus Host Location
Cryoelectron microscopy 38 Molecular biology 2

Evidence records

2 total
Experimental Infection
1 records · 1 evidence types
Evidence type Host Range Experiment
1 records
OVE4190 Host Range Experiment
Key finding

ACE2 proteins from multiple animal species bound the SARS-CoV-2 receptor binding domain and mediated SARS-CoV-2 pseudovirus transduction, demonstrating broad host-range susceptibility at the receptor level.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
animals Metazoa Experimental system
Location
Not specified
Supporting text

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.

Method
ACE2 expression screening | binding assay | pseudovirus transduction assay
Experimental system
ACE2 receptor-expression and SARS-CoV-2 pseudovirus transduction assay
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE4191 Receptor Usage
Key finding

Cryo-EM structural analysis showed that cat ACE2 binds the SARS-CoV-2 receptor-binding domain in a manner similar to human ACE2, confirming receptor usage compatibility.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
domestic cat Felis catus Experimental system human Homo sapiens Experimental system
Location
Not specified
Supporting text

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.

Method
cryo-electron microscopy | structural analysis
Receptors
ACE2