7U2E

Crystal structure of SARS-CoV-2 receptor binding domain in complex with neutralizing antibody ADI-55688

Summary for 7U2E

• Entry DOI: 10.2210/pdb7u2e/pdb
• Descriptor: Spike protein S1, ADI-55688 heavy chain, ADI-55688 light chain, ... (5 entities in total)
• Functional Keywords: sars-cov-2, coronavirus, antibody, spike, rbd, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 3
• Total formula weight: 71128.75

Authors

Yuan, M.,Zhu, X.,Wilson, I.A. (deposition date: 2022-02-23, release date: 2022-05-04, Last modification date: 2024-11-13)

Primary citation

Yuan, M.,Zhu, X.,He, W.T.,Zhou, P.,Kaku, C.I.,Capozzola, T.,Zhu, C.Y.,Yu, X.,Liu, H.,Yu, W.,Hua, Y.,Tien, H.,Peng, L.,Song, G.,Cottrell, C.A.,Schief, W.R.,Nemazee, D.,Walker, L.M.,Andrabi, R.,Burton, D.R.,Wilson, I.A.
A broad and potent neutralization epitope in SARS-related coronaviruses.
Proc.Natl.Acad.Sci.USA, 119:e2205784119-e2205784119, 2022

PubMed Abstract: Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness to SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies.

PubMed: 35767670
DOI: 10.1073/pnas.2205784119

Experimental method

X-RAY DIFFRACTION (2.85 Å)