7DDN
SARS-Cov2 S protein at open state
Summary for 7DDN
| Entry DOI | 10.2210/pdb7ddn/pdb |
| EMDB information | 30654 |
| Descriptor | Spike glycoprotein (1 entity in total) |
| Functional Keywords | sars-cov2 s protein, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) |
| Total number of polymer chains | 3 |
| Total formula weight | 420167.72 |
| Authors | |
| Primary citation | Zhang, C.,Wang, Y.,Zhu, Y.,Liu, C.,Gu, C.,Xu, S.,Wang, Y.,Zhou, Y.,Wang, Y.,Han, W.,Hong, X.,Yang, Y.,Zhang, X.,Wang, T.,Xu, C.,Hong, Q.,Wang, S.,Zhao, Q.,Qiao, W.,Zang, J.,Kong, L.,Wang, F.,Wang, H.,Qu, D.,Lavillette, D.,Tang, H.,Deng, Q.,Xie, Y.,Cong, Y.,Huang, Z. Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections. Nat Commun, 12:264-264, 2021 Cited by PubMed Abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections. PubMed: 33431876DOI: 10.1038/s41467-020-20465-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (6.3 Å) |
Structure validation
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