7t72

Epitope-based selection of SARS-CoV-2 neutralizing antibodies from convalescent patients

spinqualitylabelsall models 7t72, resolution 3.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7t72 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 3.177Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design. Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients.,Rouet R, Henry JY, Johansen MD, Sobti M, Balachandran H, Langley DB, Walker GJ, Lenthall H, Jackson J, Ubiparipovic S, Mazigi O, Schofield P, Burnett DL, Brown SHJ, Martinello M, Hudson B, Gilroy N, Post JJ, Kelleher A, Jack HM, Goodnow CC, Turville SG, Rawlinson WD, Bull RA, Stewart AG, Hansbro PM, Christ D Nat Commun. 2023 Feb 8;14(1):687. doi: 10.1038/s41467-023-36295-5. PMID:36755042 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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