7C01

Molecular basis for a potent human neutralizing antibody targeting SARS-CoV-2 RBD

Summary for 7C01

• Entry DOI: 10.2210/pdb7c01/pdb
• Descriptor: Spike protein S1, CB6 heavy chain, CB6 light chain, ... (4 entities in total)
• Functional Keywords: sars-cov-2, rbd, neutralizing antibodies, molecular basis, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 6
• Total formula weight: 149683.28

Authors

Shi, R.,Qi, J.,Wang, Q.,Gao, F.G.,Yan, J. (deposition date: 2020-04-29, release date: 2020-05-27, Last modification date: 2023-11-29)

Primary citation

Shi, R.,Shan, C.,Duan, X.,Chen, Z.,Liu, P.,Song, J.,Song, T.,Bi, X.,Han, C.,Wu, L.,Gao, G.,Hu, X.,Zhang, Y.,Tong, Z.,Huang, W.,Liu, W.J.,Wu, G.,Zhang, B.,Wang, L.,Qi, J.,Feng, H.,Wang, F.S.,Wang, Q.,Gao, G.F.,Yuan, Z.,Yan, J.
A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2.
Nature, 584:120-124, 2020

PubMed Abstract: An outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.

PubMed: 32454512
DOI: 10.1038/s41586-020-2381-y

Experimental method

X-RAY DIFFRACTION (2.88 Å)