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Literature detail

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].
PMID 34234119 2021 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

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.

Angiotensin-Converting Enzyme 2 Animals Binding Sites Cell Line Cricetinae Crystallography, X-Ray Dogs HeLa Cells Humans Mutation Protein Binding Protein Domains SARS-CoV-2 Spike Glycoprotein, Coronavirus Virus Internalization spike protein, SARS-CoV-2

Structured evidence records

Evidence records

3 total
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.90
Key finding

SARS-CoV-2 binds to dog ACE2 and infects dACE2-expressing cells, providing molecular evidence of cross-species transmission potential among domestic animals.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

SARS-CoV-2 can infect many domestic animals, including dogs... dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike protein... Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2.

Method
crystal structure determination; pseudovirus infection assay; virus binding assay
Study design
molecular binding analysis
Transmission direction
animal-to-animal
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Mutations in the SARS-CoV-2 spike receptor binding domain modulate binding affinity to dog ACE2, indicating molecular adaptation influencing cross-species transmission potential.

Virus
SARS-CoV-2
Host
Not specified
Location
Not specified
Supporting text

Dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike protein receptor binding domain (RBD), and a few important mutations in the RBD binding interface play a pivotal role in the binding affinity to both dACE2 and human ACE2.

Genes or proteins
spike; receptor binding domain
Receptors
ACE2; dog ACE2; human ACE2
Mechanism types
receptor_binding; cross_species_adaptation
Receptor Usage 1 records
Receptor Usage Extraction confidence 1.00
Key finding

SARS-CoV-2 spike RBD binds to dog ACE2 with lower affinity than human ACE2, and structural analysis confirms receptor-mediated cell entry in dACE2-expressing cells.

Virus
SARS-CoV-2
Location
Not specified
Supporting text

Dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells.

Method
crystal structure determination; pseudovirus infection assay; binding affinity analysis
Receptors
ACE2