OmniVira

Cross-species recognition of SARS-CoV-2 to bat ACE2.

Kefang Liu1,2,3 Shuguang Tan1 Sheng Niu1,4 Jia Wang5 Lili Wu1,2,6 Huan Sun1 Yanfang Zhang1,7 Xiaoqian Pan1,2 Xiao Qu1 Pei Du6 Yumin Meng1 Yunfei Jia1,4 Qian Chen1,8 Chuxia Deng3 Jinghua Yan6,9 Hong-Wei Wang5 Qihui Wang10,11,9 Jianxun Qi10,11,9 George Fu Gao10,11,9
Affiliations 11 institutions
  1. Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
  2. University of Chinese Academy of Sciences, 100049 Beijing, China.
  3. Faculty of Health Sciences, University of Macau, 999078 Macau SAR, China.
  4. College of Veterinary Medicine, Shanxi Agricultural University, 030801 Jinzhong, China.
  5. 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, 100084 Beijing, China.
  6. Chinese Academy of Sciences Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China.
  7. Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
  8. Institute of Physical Science and Information, Anhui University, 230039 Hefei, China.
  9. Savaid Medical School, University of Chinese Academy of Sciences, 100049 Beijing, China.
  10. Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101 Beijing, China
  11. [email protected] [email protected] [email protected].
PMID33335073 DOI10.1073/pnas.2020216118 Year2021 Journal Proceedings of the National Academy of Sciences of the United States of America Proc Natl Acad Sci U S A Languageeng Statusppublish

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2-related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.

Supporting text Virus Host Location
ACE2 54 COVID-19 467 RBD 13 Rhinolophus macrotis 1 SARS-CoV-2 550 Angiotensin-Converting Enzyme 2 177 Chiroptera 371 SARS-CoV-2 453 Amino Acid Substitution 81 Animals 1948 COVID-19 425 HEK293 Cells 61 Humans 1440 Mutation, Missense 26 Pandemics 108 Protein Binding 193 Protein Domains 45 Species Specificity 84 ACE2 protein, human 87

Evidence records

2 total
Experimental Infection
1 records · 1 evidence types
Evidence type Host Range Experiment
1 records
OVE4370 Host Range Experiment
Key finding

SARS-CoV-2 was experimentally shown to infect cells expressing bat ACE2 from Rhinolophus macrotis using both pseudotyped and wild-type virus assays.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
Big-eared Horseshoe Bat Rhinolophus macrotis Experimental system
Location
Not specified
Supporting text

Its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus.

Method
pseudotyped virus infectivity assay | wild-type virus infection assay
Experimental system
cell-culture system expressing bat ACE2 (bACE2-Rm)
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE4368 Receptor Usage
Key finding

SARS-CoV-2 spike receptor-binding domain binds to bat ACE2 from Rhinolophus macrotis with lower affinity than to human ACE2, and infection was supported in cells expressing bat ACE2.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
Big-eared Horseshoe Bat Rhinolophus macrotis Experimental system human Homo sapiens Experimental system
Location
Not specified
Supporting text

The SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus.

Method
binding assay | pseudovirus infection assay | structural determination | wild virus infection assay
Receptors
ACE2 | bACE2-Rm | human ACE2