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-Structure paper
タイトル | Close relatives of MERS-CoV in bats use ACE2 as their functional receptors. |
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ジャーナル・号・ページ | Nature, Vol. 612, Issue 7941, Page 748-757, Year 2022 |
掲載日 | 2022年12月7日 |
著者 | Qing Xiong / Lei Cao / Chengbao Ma / M Alejandra Tortorici / Chen Liu / Junyu Si / Peng Liu / Mengxue Gu / Alexandra C Walls / Chunli Wang / Lulu Shi / Fei Tong / Meiling Huang / Jing Li / Chufeng Zhao / Chao Shen / Yu Chen / Huabin Zhao / Ke Lan / Davide Corti / David Veesler / Xiangxi Wang / Huan Yan / |
PubMed 要旨 | Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor. However, the receptor for NeoCoV-the closest known MERS- ...Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear. Here, using a pseudotype virus entry assay, we found that NeoCoV and its close relative, PDF-2180, can efficiently bind to and use specific bat angiotensin-converting enzyme 2 (ACE2) orthologues and, less favourably, human ACE2 as entry receptors through their receptor-binding domains (RBDs) on the spike (S) proteins. Cryo-electron microscopy analysis revealed an RBD-ACE2 binding interface involving protein-glycan interactions, distinct from those of other known ACE2-using coronaviruses. We identified residues 337-342 of human ACE2 as a molecular determinant restricting NeoCoV entry, whereas a NeoCoV S pseudotyped virus containing a T510F RBD mutation efficiently entered cells expressing human ACE2. Although polyclonal SARS-CoV-2 antibodies or MERS-CoV RBD-specific nanobodies did not cross-neutralize NeoCoV or PDF-2180, an ACE2-specific antibody and two broadly neutralizing betacoronavirus antibodies efficiently inhibited these two pseudotyped viruses. We describe MERS-CoV-related viruses that use ACE2 as an entry receptor, underscoring a promiscuity of receptor use and a potential zoonotic threat. |
リンク | Nature / PubMed:36477529 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.5 - 3.8 Å |
構造データ | EMDB-26378, PDB-7u6r: EMDB-32686, PDB-7wpo: EMDB-32693, PDB-7wpz: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / Bat coronavirus / Coronavirus / PDF-2180 / spike glycoprotein / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / Merbecovirus / NeoCoV RBD / ACE2 / PDF-2180-CoV / RBD |