Literature detail

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

Shihua Li¹ Ruirui Yang^1,2 Di Zhang^1,3 Pu Han¹ Zepeng Xu^1,3 Qian Chen^1,4 Runchu Zhao^1,4 Xin Zhao^1,5 Xiao Qu¹ Anqi Zheng¹ Liang Wang^1,5 Linjie Li^1,6 Yu Hu^1,7 Rong Zhang^1,8 Chao Su¹ Sheng Niu^1,2 Yanfang Zhang¹ Jianxun Qi^1,6 Kefang Liu¹ Qihui Wang^1,2,6 George F Gao^1,2,6

Affiliations 8 institutions

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing100101, China.
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong030801, China.
Faculty of Health Sciences, University of Macau, Macau, China.
Institute of Physical Science and Information, Anhui University, Hefei230039, China.
Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing100101, China.
Savaid Medical School, University of Chinese Academy of Sciences, Beijing100049, China.
School of Life Sciences, University of Science and Technology of China, Hefei230026, China.
State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning530004, China.

PMID 36187898 2022 Natl Sci Rev eng epublish

PubMed DOI Browse context

Article

Publication summary

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.

cross-species recognition cryo-EM structure marine animals SARS-CoV-2

Structured evidence records

Evidence records

7 total

Host Range Experiment 2 records

Host Range Experiment Extraction confidence 0.85

Key finding

Marine mammal and hippopotamus ACE2 supported SARS-CoV and SARS-CoV-2 pseudovirus entry, indicating cross-species susceptibility at the receptor level.

Virus

Host

Location

Supporting text

ACE2s from several marine mammals and hippopotami could efficiently bind to the 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; ACE2-binding assay
Experimental system: pseudovirus assay

Host Range Experiment Extraction confidence 0.85

Key finding

Marine mammal and hippopotamus ACE2 supported SARS-CoV pseudovirus entry, indicating potential cross-species susceptibility similar to SARS-CoV-2.

Virus

Host

Location

Supporting text

Method: pseudovirus transduction; ACE2-binding assay
Experimental system: pseudovirus assay

Molecular Adaptation 2 records

Molecular Adaptation Extraction confidence 0.90

Key finding

SARS-CoV-2 RBD and SARS-CoV RBD showed efficient binding to ACE2 receptors from marine mammals and hippopotami, supporting a molecular adaptation enabling cross-species recognition.

Virus

Host

Location

Supporting text

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.

Genes or proteins: RBD; ACE2
Receptors: ACE2
Mechanism types: receptor_binding

Molecular Adaptation Extraction confidence 0.90

Key finding

Cryo-EM structures showed minke whale and sea lion ACE2 bound to SARS-CoV-2 and SARS-CoV RBDs in a manner similar to human ACE2, revealing structural basis for viral cross-species adaptation.

Virus

Host

Location

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.

Genes or proteins: RBD; ACE2
Receptors: ACE2
Mechanism types: receptor_binding

Receptor Usage 2 records

Receptor Usage Extraction confidence 1.00

Key finding

ACE2 receptors from marine mammals and hippopotami specifically bind the SARS-CoV and SARS-CoV-2 RBDs and mediate pseudovirus cell entry.

Virus

Host

Location

Supporting text

Method: binding assay; pseudovirus assay; cryo-electron microscopy
Receptors: ACE2

Receptor Usage Extraction confidence 1.00

Key finding

ACE2 receptors from marine mammals and hippopotami bind the SARS-CoV RBD and mediate pseudovirus cell entry similarly to human ACE2.

Virus

Host

Location

Supporting text

Method: binding assay; pseudovirus assay; cryo-electron microscopy
Receptors: ACE2

Cross Species Transmission 1 records

Cross Species Transmission Extraction confidence 0.80

Key finding

SARS-CoV and SARS-CoV-2 pseudoviruses can use ACE2 from several marine mammals including whales and sea lions, indicating potential cross-species transmission among marine mammals.

Virus

Host

Location

Supporting text

Method: pseudovirus assay; binding assay; cryo-electron microscopy
Study design: pseudovirus assay
Transmission direction: animal-to-animal

Citation context

References

48 references

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Evidence overview

Evidence 7

Types 4

Virus 2

Host 2

Evidence types

Host Range Experiment 2 Molecular Adaptation 2 Receptor Usage 2 Cross Species Transmission 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: National science review
Volume / Issue / Pages: 9 / 9 / nwac122
ISSN: 2053-714X
Journal country: China
DOI: 10.1093/nsr/nwac122