OmniVira

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

Yu Hu1,2 Kefang Liu2 Pu Han2 Zepeng Xu3 Anqi Zheng2,4 Xiaoqian Pan2,4 Yunfei Jia2,5 Chao Su2,6 Lingfeng Tang3 Lili Wu2 Bin Bai2,4 Xin Zhao2 Di Tian7 Zhihai Chen7 Jianxun Qi2,4 Qihui Wang2,4 George F Gao1,2,4
Affiliations 7 institutions
  1. School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  2. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  3. Faculty of Health Sciences, University of Macau, Macau SAR, China.
  4. University of Chinese Academy of Sciences, Beijing, China.
  5. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
  6. Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China.
  7. Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
PMID36519268 DOI10.15252/embj.2022111737 Year2023 Journal The EMBO journal EMBO J Languageeng Statusppublish

Abstract

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.

Supporting text Virus Host Location
ACE2 54 interspecies transmission 51 RBD 13 RshSTT182/200 1 SARS-CoV-2 550 Angiotensin-Converting Enzyme 2 177 Betacoronavirus 78 Chiroptera 371 Spike Glycoprotein, Coronavirus 274 Animals 1948 Host Specificity 132 Humans 1440 Protein Binding 193 Receptors, Virus 204 SARS-CoV-2 453

Evidence records

6 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Reservoir Ecology
1 records
OVE6598 Reservoir Ecology
Key finding

RshSTT182 and RshSTT200 coronaviruses were detected in Rhinolophus shameli bats in Cambodia, indicating circulation of SARS-CoV-2–related viruses in local bat populations of Southeast Asia.

Virus
SARS-related coronavirus RshSTT200
Host
Shamel's horseshoe bat Rhinolophus shameli Natural host
Location
Cambodia Southeast Asia
Supporting text

Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2.

Method
virus genome sequencing | host identification from bat specimen
Geographic raw
Cambodia | Southeast Asia
Country inferred
KHM
Experimental Infection
2 records · 1 evidence types
Evidence type Host Range Experiment
2 records
OVE6596 Host Range Experiment
Key finding

RshSTT182 pseudovirus was able to enter cells via human, fox, and Rhinolophus affinis ACE2 receptors, indicating cross-species entry capability.

Virus
SARS-related coronavirus
Host
human Homo sapiens Experimental system Vulpes Experimental system intermediate horseshoe bat Rhinolophus affinis Experimental system Shamel's horseshoe bat Rhinolophus shameli Natural host
Location
Not specified
Supporting text

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

Method
pseudovirus infection assay | receptor utilization testing | cell entry quantification
Sample type
cells expressing ACE2 receptors
Experimental system
cell-culture pseudovirus entry assay using ACE2-expressing cells
OVE6595 Host Range Experiment
Key finding

The RshSTT182/200 receptor-binding domain recognized 21 of 39 ACE2 orthologs from animal species, demonstrating broad receptor compatibility.

Virus
Sarbecovirus
Host
bats Chiroptera Experimental system Shamel's horseshoe bat Rhinolophus shameli Natural host
Location
Not specified
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
protein–protein binding assay | receptor ortholog screening | surface plasmon resonance or comparable binding quantification
Sample type
ACE2 ortholog proteins
Experimental system
receptor-binding assay using purified RBD and ACE2 orthologs
Functional Mechanism
3 records · 1 evidence types
Evidence type Receptor Usage
3 records
OVE6592 Receptor Usage
Key finding

Structural determination shows that the RshSTT182/200 coronavirus receptor binding domain directly binds human ACE2, identifying key residues influencing receptor interaction.

Virus
Sarbecovirus
Host
human Homo sapiens Experimental system
Location
Not specified
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.

Method
structural determination | crystallography | receptor binding domain (RBD)–receptor complex analysis
Receptors
human ACE2 | hACE2
OVE6594 Receptor Usage
Key finding

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

Virus
SARS-related coronavirus
Host
human Homo sapiens Experimental system Vulpes Experimental system intermediate horseshoe bat Rhinolophus affinis Experimental system
Location
Not specified
Supporting text

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

Method
pseudovirus cell entry assay | receptor utilization testing
Receptors
ACE2 receptors
OVE6593 Receptor Usage
Key finding

RshSTT182/200 receptor binding domain binds ACE2 orthologs from multiple animal species, showing broad but weaker receptor compatibility compared to SARS-CoV-2.

Virus
Sarbecovirus
Host
bats Chiroptera Experimental system
Location
Not specified
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, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2.

Method
receptor binding assay | ACE2 ortholog binding evaluation | host range analysis
Receptors
ACE2 orthologs