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TitleMolecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin.
Journal, issue, pagesEMBO J, Vol. 40, Issue 16, Page e107786, Year 2021
Publish dateAug 16, 2021
AuthorsSheng Niu / Jia Wang / Bin Bai / Lili Wu / Anqi Zheng / Qian Chen / Pei Du / Pengcheng Han / Yanfang Zhang / Yunfei Jia / Chengpeng Qiao / Jianxun Qi / Wen-Xia Tian / Hong-Wei Wang / Qihui Wang / George Fu Gao /
PubMed AbstractPangolins 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 ...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.
External linksEMBO J / PubMed:34018203 / PubMed Central
MethodsEM (single particle)
Resolution3.4 Å
Structure data

30653

7ddp

EMDB-30653, PDB-7ddp:
Cryo-EM structure of human ACE2 and GX/P2V/2017 RBD
Method: EM (single particle) / Resolution: 3.4 Å

30655

7ddo

EMDB-30655, PDB-7ddo:
Cryo-EM structure of human ACE2 and GD/1/2019 RBD
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • pangolin coronavirus
KeywordsHYDROLASE/VIRAL PROTEIN / Pangolin / RBD / ACE2 / PROTEIN BINDING / HYDROLASE-VIRAL PROTEIN complex

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