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Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin.
Niu, Sheng; Wang, Jia; Bai, Bin; Wu, Lili; Zheng, Anqi; Chen, Qian; Du, Pei; Han, Pengcheng; Zhang, Yanfang; Jia, Yunfei; Qiao, Chengpeng; Qi, Jianxun; Tian, Wen-Xia; Wang, Hong-Wei; Wang, Qihui; Gao, George Fu.
  • Niu S; College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
  • Wang J; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Bai B; Ministry of Education Key Laboratory of Protein Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center of Biological Structures, School of Life Sciences, Tsinghua University, Beijing, China.
  • Wu L; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Zheng A; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Chen Q; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Du P; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Han P; Institute of Physical Science and Information, Anhui University, Hefei, China.
  • Zhang Y; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Jia Y; Department of biomedical engineering, Emory University, Atlanta, GA, USA.
  • Qiao C; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Qi J; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
  • Tian WX; College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
  • Wang HW; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Wang Q; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Gao GF; CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
EMBO J ; 40(16): e107786, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1239217
Semantic information from SemMedBD (by NLM)
1. Basis INTERACTS_WITH ACE2 gene|ACE2
Subject
Basis
Predicate
INTERACTS_WITH
Object
ACE2 gene|ACE2
2. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
3. receptor PART_OF 2019 novel coronavirus
Subject
receptor
Predicate
PART_OF
Object
2019 novel coronavirus
4. RNA Recognition Motif INTERACTS_WITH Orthologous Gene
Subject
RNA Recognition Motif
Predicate
INTERACTS_WITH
Object
Orthologous Gene
5. Homologous Gene PART_OF House mice
Subject
Homologous Gene
Predicate
PART_OF
Object
House mice
6. Homologous Gene PART_OF Rattus norvegicus
Subject
Homologous Gene
Predicate
PART_OF
Object
Rattus norvegicus
7. Homologous Gene PART_OF European hedgehog
Subject
Homologous Gene
Predicate
PART_OF
Object
European hedgehog
8. Basis INTERACTS_WITH ACE2 gene|ACE2
Subject
Basis
Predicate
INTERACTS_WITH
Object
ACE2 gene|ACE2
9. angiotensin converting enzyme 2 PART_OF Homo sapiens
Subject
angiotensin converting enzyme 2
Predicate
PART_OF
Object
Homo sapiens
10. receptor PART_OF 2019 novel coronavirus
Subject
receptor
Predicate
PART_OF
Object
2019 novel coronavirus
11. RNA Recognition Motif INTERACTS_WITH Orthologous Gene
Subject
RNA Recognition Motif
Predicate
INTERACTS_WITH
Object
Orthologous Gene
12. Homologous Gene PART_OF House mice
Subject
Homologous Gene
Predicate
PART_OF
Object
House mice
13. Homologous Gene PART_OF Rattus norvegicus
Subject
Homologous Gene
Predicate
PART_OF
Object
Rattus norvegicus
14. Homologous Gene PART_OF European hedgehog
Subject
Homologous Gene
Predicate
PART_OF
Object
European hedgehog
ABSTRACT
Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin-converting enzyme 2 (hACE2), the receptor of SARS-CoV-2. We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoV RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells. A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD. Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat, and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Betacoronavirus / Angiotensin-Converting Enzyme 2 / Pangolins / SARS-CoV-2 Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: EMBO J Year: 2021 Document Type: Article Affiliation country: Embj.2021107786

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / Betacoronavirus / Angiotensin-Converting Enzyme 2 / Pangolins / SARS-CoV-2 Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: EMBO J Year: 2021 Document Type: Article Affiliation country: Embj.2021107786