7CHH

Cryo-EM structure of the SARS-CoV-2 S-6P in complex with BD-368-2 Fabs

Summary for 7CHH

• Entry DOI: 10.2210/pdb7chh/pdb
• EMDB information: 30374
• Descriptor: Spike glycoprotein, BD-368-2 Fab heavy chain, BD-368-2 Fab light chain, ... (5 entities in total)
• Functional Keywords: sars-cov-2 spike, neutralizing antibody, antiviral protein-immune system complex, antiviral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 9
• Total formula weight: 555096.83

Authors

Xiao, J.,Zhu, Q.,Wang, G. (deposition date: 2020-07-05, release date: 2020-09-16, Last modification date: 2024-10-30)

Primary citation

Du, S.,Cao, Y.,Zhu, Q.,Yu, P.,Qi, F.,Wang, G.,Du, X.,Bao, L.,Deng, W.,Zhu, H.,Liu, J.,Nie, J.,Zheng, Y.,Liang, H.,Liu, R.,Gong, S.,Xu, H.,Yisimayi, A.,Lv, Q.,Wang, B.,He, R.,Han, Y.,Zhao, W.,Bai, Y.,Qu, Y.,Gao, X.,Ji, C.,Wang, Q.,Gao, N.,Huang, W.,Wang, Y.,Xie, X.S.,Su, X.D.,Xiao, J.,Qin, C.
Structurally Resolved SARS-CoV-2 Antibody Shows High Efficacy in Severely Infected Hamsters and Provides a Potent Cocktail Pairing Strategy.
Cell, 183:1013-1023.e13, 2020

PubMed Abstract: Understanding how potent neutralizing antibodies (NAbs) inhibit SARS-CoV-2 is critical for effective therapeutic development. We previously described BD-368-2, a SARS-CoV-2 NAb with high potency; however, its neutralization mechanism is largely unknown. Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their "up" or "down" conformations. Also, BD-368-2 treats infected adult hamsters at low dosages and at various administering windows, in contrast to placebo hamsters that manifested severe interstitial pneumonia. Moreover, BD-368-2's epitope completely avoids the common binding site of VH3-53/VH3-66 recurrent NAbs, evidenced by tripartite co-crystal structures with RBDs. Pairing BD-368-2 with a potent recurrent NAb neutralizes SARS-CoV-2 pseudovirus at pM level and rescues mutation-induced neutralization escapes. Together, our results rationalized a new RBD epitope that leads to high neutralization potency and demonstrated BD-368-2's therapeutic potential in treating COVID-19.

PubMed: 32970990
DOI: 10.1016/j.cell.2020.09.035

Experimental method

ELECTRON MICROSCOPY (3.49 Å)