7dcc: Difference between revisions
m Protected "7dcc" [edit=sysop:move=sysop] |
No edit summary |
||
| (3 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==S-3C1-F3b structure, all the three RBDs are in the up conformation and each of them associates with a 3C1 Fab== | ||
<StructureSection load='7dcc' size='340' side='right'caption='[[7dcc]], [[Resolution|resolution]] 4.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7dcc]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DCC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.3Å</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7dcc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dcc OCA], [https://pdbe.org/7dcc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dcc RCSB], [https://www.ebi.ac.uk/pdbsum/7dcc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dcc ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 A 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. | |||
Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.,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 Nat Commun. 2021 Jan 11;12(1):264. doi: 10.1038/s41467-020-20465-w. PMID:33431876<ref>PMID:33431876</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7dcc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Cong Y]] | |||
[[Category: Liu CX]] | |||
Latest revision as of 11:40, 17 October 2024
S-3C1-F3b structure, all the three RBDs are in the up conformation and each of them associates with a 3C1 FabS-3C1-F3b structure, all the three RBDs are in the up conformation and each of them associates with a 3C1 Fab
Structural highlights
Publication Abstract from PubMedThe 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 A 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. Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections.,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 Nat Commun. 2021 Jan 11;12(1):264. doi: 10.1038/s41467-020-20465-w. PMID:33431876[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||