OmniVira

The molecular basis for SARS-CoV-2 binding to dog ACE2.

Zengyuan Zhang1,2 Yanfang Zhang1,3 Kefang Liu1 Yan Li1 Qiong Lu4 Qingling Wang5 Yuqin Zhang1,2 Liang Wang1 Hanyi Liao1,2 Anqi Zheng1,2 Sufang Ma1 Zheng Fan6 Huifang Li7 Weijin Huang4 Yuhai Bi1 Xin Zhao1 Qihui Wang1 George F Gao8 Haixia Xiao9 Zhou Tong10 Jianxun Qi11,12 Yeping Sun13
Affiliations 13 institutions
  1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  2. University of Chinese Academy of Sciences, Beijing, China.
  3. Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
  4. Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control (NIFDC), Beijing, China.
  5. Shanxi Natural Carbohydrate Resource Engineering Research Center, College of Food Science and Technology, Northwest University, Xi'an, China.
  6. Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  7. The Northern Medical District of the PLA General Hospital, Beijing, China.
  8. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
  9. Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. [email protected].
  10. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
  11. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
  12. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China. [email protected].
  13. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China. [email protected].
PMID34234119 DOI10.1038/s41467-021-24326-y Year2021 Journal Nature communications Nat Commun Languageeng Statusepublish

Abstract

SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.

Supporting text Virus Host Location
Angiotensin-Converting Enzyme 2 177 Animals 1948 Binding Sites 89 Cell Line 158 Cricetinae 41 Crystallography, X-Ray 32 Dogs 176 HeLa Cells 13 Humans 1440 Mutation 209 Protein Binding 193 Protein Domains 45 SARS-CoV-2 453 Spike Glycoprotein, Coronavirus 274 Virus Internalization 100 spike protein, SARS-CoV-2 157

Evidence records

1 total
Experimental Infection
1 records · 1 evidence types
Evidence type Host Range Experiment
1 records
OVE4954 Host Range Experiment
Key finding

Both pseudotyped and authentic SARS-CoV-2 were able to infect dog ACE2-expressing cells, demonstrating that canine ACE2 supports viral entry.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
dog Canis lupus familiaris Experimental system
Location
Not specified
Supporting text

Both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells.

Method
pseudovirus infection assay | authentic virus infection assay
Experimental system
ACE2 receptor-expression cell system