8zhq

SFTSV Gn in complex with JK-8/12 Fab

spinqualitylabelsall models 8zhq, resolution 2.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8zhq is a 5 chain structure with sequence from Homo sapiens and Severe fever with thrombocytopenia syndrome virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.37Å Ligands: MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A2Z4HIM0_SFTS Publication Abstract from PubMed BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne phlebovirus that causes viral hemorrhagic fever. Pandemic concerns have arisen due to the increased human-to-human transmission and high mortality rate, highlighting the urgent need for specific therapeutics. METHODS: Our observational study characterized the memory B cell response to natural SFTSV infection in four survivors. Monoclonal antibodies (mAbs) targeting the SFTSV glycoprotein N (Gn) were isolated and tested for in vitro neutralizing activities and effects on virus binding. Structural analysis was performed to identify neutralizing epitopes recognized by the mAbs. Prophylactical and therapeutical protections were evaluated using a lethal SFTSV infection model. FINDINGS: The selected mAbs exhibiting neutralizing activity primarily originate from the IGHV5-51 and IGHV3-30 germlines and target four distinct antigenic sites on SFTSV Gn. These elite mAbs effectively blocked the interaction between Gn and the cell receptor, preventing infections from five phylogenetically distinct SFTSV clades. Structural analysis revealed a novel neutralizing epitope located within SFTSV Gn domain I recognized by the elite mAbs. In mice of lethal infections with different SFTSV strains, administering a low dose of elite mAbs significantly improved survival rates in both prophylactic and therapeutic settings. INTERPRETATION: This study identifies potent broadly neutralizing antibodies that holds promise for use in humans against SFTSV infection and highlights inhibition of receptor binding as a crucial mechanism for effective antibody-mediated neutralization against phleboviruses. FUNDING: The National Key Research and Development Plan of China (2018YFE0200401, 2022YFC2303300), National Natural Science Foundation of China (81825019), China Postdoctoral Science Foundation (2023M741824). Discovery and characterization of potent broadly neutralizing antibodies from human survivors of severe fever with thrombocytopenia syndrome.,Zhang S, Shang H, Han S, Li J, Peng X, Wu Y, Yang X, Leng Y, Wang F, Cui N, Xu L, Zhang H, Guo Y, Xu X, Zhang N, Liu W, Li H EBioMedicine. 2024 Dec 6;111:105481. doi: 10.1016/j.ebiom.2024.105481. PMID:39644769 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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