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-Structure paper
タイトル | Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin. |
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ジャーナル・号・ページ | EMBO J, Vol. 40, Issue 16, Page e107786, Year 2021 |
掲載日 | 2021年8月16日 |
著者 | Sheng 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 要旨 | 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 ...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. |
リンク | EMBO J / PubMed:34018203 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 Å |
構造データ | EMDB-30653, PDB-7ddp: EMDB-30655, PDB-7ddo: |
化合物 | ChemComp-ZN: ChemComp-NAG: |
由来 |
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キーワード | HYDROLASE/VIRAL PROTEIN / Pangolin / RBD / ACE2 / PROTEIN BINDING / HYDROLASE-VIRAL PROTEIN complex |