OmniVira

Binding and structural basis of equine ACE2 to RBDs from SARS-CoV, SARS-CoV-2 and related coronaviruses.

Zepeng Xu1,2 Xinrui Kang1,3 Pu Han1 Pei Du1 Linjie Li1,4 Anqi Zheng1,4 Chuxia Deng2 Jianxun Qi1,4 Xin Zhao1 Qihui Wang5,6 Kefang Liu7 George Fu Gao1
Affiliations 7 institutions
  1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
  2. Faculty of Health Sciences, University of Macau, Macau SAR, 999078, China.
  3. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China.
  4. University of Chinese Academy of Sciences, Beijing, 100049, China.
  5. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. [email protected].
  6. University of Chinese Academy of Sciences, Beijing, 100049, China. [email protected].
  7. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. [email protected].
PMID35729237 DOI10.1038/s41467-022-31276-6 Year2022 Journal Nature communications Nat Commun Languageeng Statusepublish

Abstract

The origin and host range of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), are important scientific questions as they might provide insight into understanding of the potential future spillover to infect humans. Here, we tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin coronavirus (CoV) RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019. We also determined the crystal structures of eqACE2/RaTG13-RBD, eqACE2/SARS-CoV-2 PT-RBD and eqACE2/Omicron BA.1-RBD. We identified S494 of SARS-COV-2 PT-RBD as an important residue in the eqACE2/SARS-COV-2 PT-RBD interaction and found that N501Y, the commonly recognized enhancing mutation, attenuated the binding affinity with eqACE2. Our work demonstrates that horses are potential targets for SARS-CoV-2 and highlights the importance of continuous surveillance on SARS-CoV-2 and related CoVs to prevent spillover events.

Supporting text Virus Host Location
Angiotensin-Converting Enzyme 2 177 COVID-19 425 Animals 1948 Horses 52 Peptidyl-Dipeptidase A 57 Protein Binding 193 SARS-CoV-2 453 Spike Glycoprotein, Coronavirus 274 spike protein, SARS-CoV-2 157

Evidence records

2 total
Experimental Infection
1 records · 1 evidence types
Evidence type Host Range Experiment
1 records
OVE6088 Host Range Experiment
Key finding

Equine ACE2 bound to the receptor binding domains of SARS-CoV-2 and related coronaviruses, indicating horses may be susceptible to SARS-CoV-2 infection.

Virus
Severe acute respiratory syndrome coronavirus 2 Severe Acute Respiratory Syndrome Coronavirus SARS-related coronavirus GD/1/2019
Host
horse Equus caballus Experimental system bats Chiroptera Natural host pangolins Manidae Natural host
Location
Not specified
Supporting text

We tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs)... Our work demonstrates that horses are potential targets for SARS-CoV-2.

Method
binding assay | crystallography | structural modeling
Sample type
receptor binding domains | ACE2 protein
Experimental system
in vitro receptor-binding and structural (crystallography) system using equine ACE2 and virus RBDs
Functional Mechanism
1 records · 1 evidence types
Evidence type Molecular Adaptation
1 records
OVE6087 Molecular Adaptation
Key finding

Residue S494 enhances interaction between SARS-CoV-2 PT-RBD and the equine ACE2 receptor, while the N501Y mutation reduces binding affinity with eqACE2.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
Not specified
Location
Not specified
Supporting text

We identified S494 of SARS-COV-2 PT-RBD as an important residue in the eqACE2/SARS-COV-2 PT-RBD interaction and found that N501Y, the commonly recognized enhancing mutation, attenuated the binding affinity with eqACE2.

Genes or proteins
RBD | Spike protein
Receptors
equine angiotensin converting enzyme 2 (eqACE2)
Host factors
eqACE2
Mutations
S494 | N501Y
Mechanism types
receptor binding | host-range expansion