7LM9

Crystal structure of SARS-CoV spike protein receptor-binding domain in complex with a cross-neutralizing antibody CV38-142 Fab isolated from COVID-19 patient

Summary for 7LM9

• Entry DOI: 10.2210/pdb7lm9/pdb
• Descriptor: Spike glycoprotein, CV38-142 Fab heavy chain, CV38-142 Fab light chain, ... (6 entities in total)
• Functional Keywords: sars-cov, antibody, spike, coronavirus, sars, immune system, viral protein-immune system complex, cross-neutralization, viral protein, viral protein/immune system
• Biological source: SARS coronavirus MA15; More
• Total number of polymer chains: 3
• Total formula weight: 75148.97

Authors

Liu, H.,Yuan, M.,Zhu, X.,Wilson, I.A. (deposition date: 2021-02-05, release date: 2021-03-31, Last modification date: 2023-10-18)

Primary citation

Liu, H.,Yuan, M.,Huang, D.,Bangaru, S.,Zhao, F.,Lee, C.D.,Peng, L.,Barman, S.,Zhu, X.,Nemazee, D.,Burton, D.R.,van Gils, M.J.,Sanders, R.W.,Kornau, H.C.,Reincke, S.M.,Pruss, H.,Kreye, J.,Wu, N.C.,Ward, A.B.,Wilson, I.A.
A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection.
Cell Host Microbe, 29:806-818.e6, 2021

PubMed Abstract: Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody, CV38-142, in complex with the receptor-binding domains from SARS-CoV-2 and SARS-CoV. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic SARS-related coronaviruses.

PubMed: 33894127
DOI: 10.1016/j.chom.2021.04.005

Experimental method

X-RAY DIFFRACTION (1.53 Å)