OmniVira

Cross-species recognition and molecular basis of SARS-CoV-2 and SARS-CoV binding to ACE2s of marine animals.

Shihua Li1 Ruirui Yang1,2 Di Zhang1,3 Pu Han1 Zepeng Xu1,3 Qian Chen1,4 Runchu Zhao1,4 Xin Zhao1,5 Xiao Qu1 Anqi Zheng1 Liang Wang1,5 Linjie Li1,6 Yu Hu1,7 Rong Zhang1,8 Chao Su1 Sheng Niu1,2 Yanfang Zhang1 Jianxun Qi1,6 Kefang Liu1 Qihui Wang1,2,6 George F Gao1,2,6
Affiliations 8 institutions
  1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing100101, China.
  2. College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong030801, China.
  3. Faculty of Health Sciences, University of Macau, Macau, China.
  4. Institute of Physical Science and Information, Anhui University, Hefei230039, China.
  5. Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing100101, China.
  6. Savaid Medical School, University of Chinese Academy of Sciences, Beijing100049, China.
  7. School of Life Sciences, University of Science and Technology of China, Hefei230026, China.
  8. State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning530004, China.
PMID36187898 DOI10.1093/nsr/nwac122 Year2022 Journal National science review Natl Sci Rev Languageeng Statusepublish

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has an extremely broad host range that includes hippopotami, which are phylogenetically closely related to whales. The cellular ACE2 receptor is one of the key determinants of the host range. Here, we found that ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of both SARS-CoV and SARS-CoV-2 and facilitate the transduction of SARS-CoV and SARS-CoV-2 pseudoviruses into ACE2-expressing cells. We further resolved the cryo-electron microscopy complex structures of the minke whale ACE2 and sea lion ACE2, respectively, bound to the RBDs, revealing that they have similar binding modes to human ACE2 when it comes to the SARS-CoV-2 RBD and SARS-CoV RBD. Our results indicate that marine mammals could potentially be new victims or virus carriers of SARS-CoV-2, which deserves further careful investigation and study. It will provide an early warning for the prospective monitoring of marine mammals.

Supporting text Virus Host Location
cross-species recognition 2 cryo-EM structure 9 marine animals 1 SARS-CoV-2 550

Evidence records

4 total
Experimental Infection
2 records · 1 evidence types
Evidence type Host Range Experiment
2 records
OVE6415 Host Range Experiment
Key finding

ACE2s from marine mammals and hippopotami facilitated entry of SARS-CoV-2 pseudoviruses, indicating potential host susceptibility.

Virus
Severe acute respiratory syndrome coronavirus 2
Host
mammals Mammalia Experimental system hippopotamus Hippopotamus amphibius Experimental system
Location
Not specified
Supporting text

ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of SARS-CoV-2 and facilitate the transduction of SARS-CoV-2 pseudoviruses into ACE2-expressing cells.

Method
pseudovirus transduction assay | receptor-binding domain interaction analysis | cryo-electron microscopy structural analysis
Experimental system
ACE2-expressing cell pseudovirus transduction assay
OVE6414 Host Range Experiment
Key finding

ACE2s from marine mammals and hippopotami facilitated entry of SARS-CoV pseudoviruses, demonstrating receptor-mediated susceptibility in pseudovirus assays.

Virus
Severe Acute Respiratory Syndrome Coronavirus
Host
mammals Mammalia Experimental system hippopotamus Hippopotamus amphibius Experimental system
Location
Not specified
Supporting text

ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of SARS-CoV and facilitate the transduction of SARS-CoV pseudoviruses into ACE2-expressing cells.

Method
pseudovirus transduction assay | receptor-binding domain interaction analysis
Experimental system
ACE2-expressing cell pseudovirus transduction assay
Functional Mechanism
2 records · 1 evidence types
Evidence type Receptor Usage
2 records
OVE6412 Receptor Usage
Key finding

ACE2 receptors from marine mammals and hippopotami efficiently bind SARS-CoV and SARS-CoV-2 receptor-binding domains and mediate pseudovirus entry.

Virus
Severe Acute Respiratory Syndrome Coronavirus Severe acute respiratory syndrome coronavirus 2
Host
mammals Mammalia Experimental system hippopotamus Hippopotamus amphibius Experimental system
Location
Not specified
Supporting text

Here, we found that ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of both SARS-CoV and SARS-CoV-2 and facilitate the transduction of SARS-CoV and SARS-CoV-2 pseudoviruses into ACE2-expressing cells.

Method
pseudovirus transduction assay | receptor-binding assay
Receptors
ACE2
OVE6413 Receptor Usage
Key finding

Cryo-electron microscopy structures reveal that minke whale ACE2 and sea lion ACE2 bind SARS-CoV and SARS-CoV-2 RBDs with modes similar to human ACE2.

Virus
Severe Acute Respiratory Syndrome Coronavirus Severe acute respiratory syndrome coronavirus 2
Host
minke whale Balaenoptera acutorostrata Experimental system fur seals & sea lions Otariidae Experimental system human Homo sapiens Experimental system
Location
Not specified
Supporting text

We further resolved the cryo-electron microscopy complex structures of the minke whale ACE2 and sea lion ACE2, respectively, bound to the RBDs, revealing that they have similar binding modes to human ACE2 when it comes to the SARS-CoV-2 RBD and SARS-CoV RBD.

Method
cryo-electron microscopy structural analysis
Receptors
ACE2