7V61

ACE2 -Targeting Monoclonal Antibody as Potent and Broad-Spectrum Coronavirus Blocker

Summary for 7V61

• Entry DOI: 10.2210/pdb7v61/pdb
• EMDB information: 31732
• Descriptor: Sodium-dependent neutral amino acid transporter B(0)AT1, Angiotensin-converting enzyme 2, 3E8, ... (8 entities in total)
• Functional Keywords: ace2-b0at1 complex, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 489753.78

Authors

Yan, R.H.,Zhang, Y.Y.,Li, Y.N.,Zhou, Q. (deposition date: 2021-08-18, release date: 2022-06-22, Last modification date: 2024-11-13)

Primary citation

Chen, Y.,Zhang, Y.N.,Yan, R.,Wang, G.,Zhang, Y.,Zhang, Z.R.,Li, Y.,Ou, J.,Chu, W.,Liang, Z.,Wang, Y.,Chen, Y.L.,Chen, G.,Wang, Q.,Zhou, Q.,Zhang, B.,Wang, C.
ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker.
Signal Transduct Target Ther, 6:315-315, 2021

PubMed Abstract: The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 "knock-in" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and "alanine walk" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and "broad-spectrum" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.

PubMed: 34433803
DOI: 10.1038/s41392-021-00740-y

Experimental method

ELECTRON MICROSCOPY (3.2 Å)