8qq0

SARS-CoV-2 S protein bound to neutralising antibody UZGENT_A3

spinqualitylabelsall models 8qq0, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8qq0 is a 3 chain structure with sequence from Escherichia virus T4, Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.5Å Ligands: FUC, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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