7WPO

Structure of NeoCOV RBD binding to Bat37 ACE2

Summary for 7WPO

• Entry DOI: 10.2210/pdb7wpo/pdb
• EMDB information: 32686
• Descriptor: Angiotensin-converting enzyme, Spike glycoprotein, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: merbecovirus, neocov rbd, ace2, viral protein
• Biological source: Pipistrellus pipistrellus (common pipistrelle); More
• Total number of polymer chains: 2
• Total formula weight: 106053.80

Authors

Cao, L.,Wang, X.,Tortorici, M.A.,Veesler, D. (deposition date: 2022-01-24, release date: 2022-11-30, Last modification date: 2024-11-20)

Primary citation

Xiong, Q.,Cao, L.,Ma, C.,Tortorici, M.A.,Liu, C.,Si, J.,Liu, P.,Gu, M.,Walls, A.C.,Wang, C.,Shi, L.,Tong, F.,Huang, M.,Li, J.,Zhao, C.,Shen, C.,Chen, Y.,Zhao, H.,Lan, K.,Corti, D.,Veesler, D.,Wang, X.,Yan, H.
Close relatives of MERS-CoV in bats use ACE2 as their functional receptors.
Nature, 612:748-757, 2022

PubMed Abstract: 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.

PubMed: 36477529
DOI: 10.1038/s41586-022-05513-3

Experimental method

ELECTRON MICROSCOPY (3.5 Å)