View source for 8qq0


==SARS-CoV-2 S protein bound to neutralising antibody UZGENT_A3==
<StructureSection load='8qq0' size='340' side='right'caption='[[8qq0]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qq0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4], [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=8QQ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QQ0 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]] 3.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <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=8qq0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qq0 OCA], [https://pdbe.org/8qq0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qq0 RCSB], [https://www.ebi.ac.uk/pdbsum/8qq0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qq0 ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
BACKGROUND: SARS-CoV-2-neutralizing antibodies (nABs) showed great promise in the early phases of the COVID-19 pandemic. The emergence of resistant strains, however, quickly rendered the majority of clinically approved nABs ineffective. This underscored the imperative to develop nAB cocktails targeting non-overlapping epitopes. METHODS: Undertaking a nAB discovery program, we employed a classical workflow, while integrating artificial intelligence (AI)-based prediction to select non-competing nABs very early in the pipeline. We identified and in vivo validated (in female Syrian hamsters) two highly potent nABs. FINDINGS: Despite the promising results, in depth cryo-EM structural analysis demonstrated that the AI-based prediction employed with the intention to ensure non-overlapping epitopes was inaccurate. The two nABs in fact bound to the same receptor-binding epitope in a remarkably similar manner. INTERPRETATION: Our findings indicate that, even in the Alphafold era, AI-based predictions of paratope-epitope interactions are rough and experimental validation of epitopes remains an essential cornerstone of a successful nAB lead selection. FUNDING: Full list of funders is provided at the end of the manuscript.

Integrating artificial intelligence-based epitope prediction in a SARS-CoV-2 antibody discovery pipeline: caution is warranted.,Acar DD, Witkowski W, Wejda M, Wei R, Desmet T, Schepens B, De Cae S, Sedeyn K, Eeckhaut H, Fijalkowska D, Roose K, Vanmarcke S, Poupon A, Jochmans D, Zhang X, Abdelnabi R, Foo CS, Weynand B, Reiter D, Callewaert N, Remaut H, Neyts J, Saelens X, Gerlo S, Vandekerckhove L EBioMedicine. 2024 Feb;100:104960. doi: 10.1016/j.ebiom.2023.104960. Epub 2024 , Jan 16. PMID:38232633<ref>PMID:38232633</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia virus T4]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Acar DD]]
[[Category: Gerlo S]]
[[Category: Reiter D]]
[[Category: Remaut H]]
[[Category: Vandenkerckhove L]]
[[Category: Witkowski W]]