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==== | ==Structure of the SARS-CoV-2 spike glycoprotein in complex with a human single domain antibody n3113 (UDD-state, state 1)== | ||
<StructureSection load='7vnc' size='340' side='right'caption='[[7vnc]]' scene=''> | <StructureSection load='7vnc' size='340' side='right'caption='[[7vnc]], [[Resolution|resolution]] 3.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7vnc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7VNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VNC FirstGlance]. <br> | ||
</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=7vnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vnc OCA], [https://pdbe.org/7vnc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vnc RCSB], [https://www.ebi.ac.uk/pdbsum/7vnc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vnc ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7vnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vnc OCA], [https://pdbe.org/7vnc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vnc RCSB], [https://www.ebi.ac.uk/pdbsum/7vnc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vnc ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19. | |||
A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants.,Yang Z, Wang Y, Jin Y, Zhu Y, Wu Y, Li C, Kong Y, Song W, Tian X, Zhan W, Huang A, Zhou S, Xia S, Tian X, Peng C, Chen C, Shi Y, Hu G, Du S, Wang Y, Xie Y, Jiang S, Lu L, Sun L, Song Y, Ying T Signal Transduct Target Ther. 2021 Nov 3;6(1):378. doi: , 10.1038/s41392-021-00810-1. PMID:34732694<ref>PMID:34732694</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7vnc" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Z | [[Category: Severe acute respiratory syndrome coronavirus 2]] | ||
[[Category: Jin Y]] | |||
[[Category: Kong Y]] | |||
[[Category: Wang Y]] | |||
[[Category: Wu Y]] | |||
[[Category: Yang Z]] | |||
[[Category: Ying T]] | |||
Latest revision as of 12:39, 9 October 2024
Structure of the SARS-CoV-2 spike glycoprotein in complex with a human single domain antibody n3113 (UDD-state, state 1)Structure of the SARS-CoV-2 spike glycoprotein in complex with a human single domain antibody n3113 (UDD-state, state 1)
Structural highlights
Publication Abstract from PubMedThe current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19. A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants.,Yang Z, Wang Y, Jin Y, Zhu Y, Wu Y, Li C, Kong Y, Song W, Tian X, Zhan W, Huang A, Zhou S, Xia S, Tian X, Peng C, Chen C, Shi Y, Hu G, Du S, Wang Y, Xie Y, Jiang S, Lu L, Sun L, Song Y, Ying T Signal Transduct Target Ther. 2021 Nov 3;6(1):378. doi: , 10.1038/s41392-021-00810-1. PMID:34732694[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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