7u09

Crystal Structure of C13B8 Fab in complex with SARS-CoV-2 S fusion peptide

spinqualitylabelsall models 7u09, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7u09 is a 3 chain structure with sequence from 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: X-ray diffraction, Resolution 2.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide-specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs. ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.,Low JS, Jerak J, Tortorici MA, McCallum M, Pinto D, Cassotta A, Foglierini M, Mele F, Abdelnabi R, Weynand B, Noack J, Montiel-Ruiz M, Bianchi S, Benigni F, Sprugasci N, Joshi A, Bowen JE, Stewart C, Rexhepaj M, Walls AC, Jarrossay D, Morone D, Paparoditis P, Garzoni C, Ferrari P, Ceschi A, Neyts J, Purcell LA, Snell G, Corti D, Lanzavecchia A, Veesler D, Sallusto F Science. 2022 Aug 12;377(6607):735-742. doi: 10.1126/science.abq2679. Epub 2022 , Jul 12. PMID:35857703 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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