Literature detail

Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs.

Yu Hu^1,2 Kefang Liu² Pu Han² Zepeng Xu³ Anqi Zheng^2,4 Xiaoqian Pan^2,4 Yunfei Jia^2,5 Chao Su^2,6 Lingfeng Tang³ Lili Wu² Bin Bai^2,4 Xin Zhao² Di Tian⁷ Zhihai Chen⁷ Jianxun Qi^2,4 Qihui Wang^2,4 George F Gao^1,2,4

Affiliations 7 institutions

School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Faculty of Health Sciences, University of Macau, Macau SAR, China.
University of Chinese Academy of Sciences, Beijing, China.
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China.
Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

PMID 36519268 2023 EMBO J eng ppublish

PubMed DOI Browse context

Article

Publication summary

Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor-binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, these findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.

ACE2 interspecies transmission RBD RshSTT182/200 SARS-CoV-2 Angiotensin-Converting Enzyme 2 Betacoronavirus Chiroptera Spike Glycoprotein, Coronavirus Animals Host Specificity Humans Protein Binding Receptors, Virus SARS-CoV-2

Structured evidence records

Evidence records

8 total

Receptor Usage 5 records

Receptor Usage Extraction confidence 1.00

Key finding

The RshSTT182/200 coronavirus RBD binds human ACE2 and specific contact residues were identified.

Virus

Host

Location

Supporting text

We determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified key residues that influence receptor binding.

Method: structural analysis
Receptors: human ACE2

Receptor Usage Extraction confidence 1.00

Key finding

RshSTT182/200 coronavirus RBD can bind ACE2 orthologs from 21 of 39 tested animal species.

Virus

Host

Location

Supporting text

The binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs.

Method: binding assay
Receptors: ACE2 orthologs

Receptor Usage Extraction confidence 1.00

Key finding

RshSTT182 pseudovirus uses ACE2 from human, fox, and Rhinolophus affinis for cell entry.

Virus

Host

Location

Supporting text

RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry.

Method: pseudovirus assay
Receptors: ACE2

Receptor Usage Extraction confidence 1.00

Key finding

RshSTT182 pseudovirus uses fox ACE2 for cell entry.

Virus

Host

Location

Supporting text

RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry.

Method: pseudovirus assay
Receptors: ACE2

Receptor Usage Extraction confidence 1.00

Key finding

RshSTT182 pseudovirus uses Rhinolophus affinis ACE2 for cell entry.

Virus

Host

Location

Supporting text

RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry.

Method: pseudovirus assay
Receptors: ACE2

Host Range Experiment 1 records

Host Range Experiment Extraction confidence 0.95

Key finding

Pseudovirus assays demonstrated that RshSTT182 coronavirus can enter cells via human, fox, and Rhinolophus affinis ACE2 receptors, indicating cross-species infection potential.

Virus

Host

Location

Supporting text

RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry.

Method: cell-entry assay
Experimental system: pseudovirus assay

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.90

Key finding

Structural and functional analysis revealed that the RshSTT182/200 coronavirus spike RBD possesses amino-acid features enabling binding to human and various animal ACE2 receptors, mediating cell entry and defining molecular determinants of host adaptation.

Virus

Host

Location

Supporting text

We determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. RshSTT182/200 RBD broadly recognized 21 of 39 ACE2 orthologs, and RshSTT182 pseudovirus could utilize human, fox, and Rhinolophus affinis ACE2 receptors for cell entry.

Genes or proteins: RBD; Spike Glycoprotein
Receptors: ACE2
Mechanism types: receptor_binding; cell_entry; host_range

Serological Evidence 1 records

Serological Evidence Extraction confidence 0.80

Key finding

SARS-CoV-2 infection generates cross-neutralizing antibodies that react against the bat-origin RshSTT182 pseudovirus, indicating serological cross-reactivity between the two coronaviruses.

Virus

Host

Location

Supporting text

Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus.

Method: neutralization test
Sample type: serum

Citation context

References

56 references

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Evidence overview

Evidence 8

Types 4

Virus 1

Host 5

Evidence types

Receptor Usage 5 Host Range Experiment 1 Molecular Adaptation 1 Serological Evidence 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: The EMBO journal
Volume / Issue / Pages: 42 / 4 / e111737
ISSN: 1460-2075
Journal country: England
DOI: 10.15252/embj.2022111737