tetano
Editor, Senior Moderator
Nature
. 2022 Dec 7.
doi: 10.1038/s41586-022-05513-3. Online ahead of print.
Close relatives of MERS-CoV in bats use ACE2 as their functional receptors
Qing Xiong[SUP] #[/SUP][SUP] 1 [/SUP], Lei Cao[SUP] #[/SUP][SUP] 2 [/SUP], Chengbao Ma[SUP] #[/SUP][SUP] 1 [/SUP], M Alejandra Tortorici[SUP] #[/SUP][SUP] 3 [/SUP], Chen Liu[SUP] 1 [/SUP], Junyu Si[SUP] 1 [/SUP], Peng Liu[SUP] 1 [/SUP], Mengxue Gu[SUP] 1 [/SUP], Alexandra C Walls[SUP] 3 4 [/SUP], Chunli Wang[SUP] 1 [/SUP], Lulu Shi[SUP] 1 [/SUP], Fei Tong[SUP] 1 [/SUP], Meiling Huang[SUP] 1 [/SUP], Jing Li[SUP] 1 [/SUP], Chufeng Zhao[SUP] 1 [/SUP], Chao Shen[SUP] 1 [/SUP], Yu Chen[SUP] 1 [/SUP], Huabin Zhao[SUP] 5 [/SUP], Ke Lan[SUP] 1 [/SUP], Davide Corti[SUP] 6 [/SUP], David Veesler[SUP] 7 8 [/SUP], Xiangxi Wang[SUP] 9 10 [/SUP], Huan Yan[SUP] 11 [/SUP]
Affiliations
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor[SUP]1-4[/SUP]. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear[SUP]5[/SUP]. 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.
. 2022 Dec 7.
doi: 10.1038/s41586-022-05513-3. Online ahead of print.
Close relatives of MERS-CoV in bats use ACE2 as their functional receptors
Qing Xiong[SUP] #[/SUP][SUP] 1 [/SUP], Lei Cao[SUP] #[/SUP][SUP] 2 [/SUP], Chengbao Ma[SUP] #[/SUP][SUP] 1 [/SUP], M Alejandra Tortorici[SUP] #[/SUP][SUP] 3 [/SUP], Chen Liu[SUP] 1 [/SUP], Junyu Si[SUP] 1 [/SUP], Peng Liu[SUP] 1 [/SUP], Mengxue Gu[SUP] 1 [/SUP], Alexandra C Walls[SUP] 3 4 [/SUP], Chunli Wang[SUP] 1 [/SUP], Lulu Shi[SUP] 1 [/SUP], Fei Tong[SUP] 1 [/SUP], Meiling Huang[SUP] 1 [/SUP], Jing Li[SUP] 1 [/SUP], Chufeng Zhao[SUP] 1 [/SUP], Chao Shen[SUP] 1 [/SUP], Yu Chen[SUP] 1 [/SUP], Huabin Zhao[SUP] 5 [/SUP], Ke Lan[SUP] 1 [/SUP], Davide Corti[SUP] 6 [/SUP], David Veesler[SUP] 7 8 [/SUP], Xiangxi Wang[SUP] 9 10 [/SUP], Huan Yan[SUP] 11 [/SUP]
Affiliations
- PMID: 36477529
- DOI: 10.1038/s41586-022-05513-3
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor[SUP]1-4[/SUP]. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear[SUP]5[/SUP]. 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.