21au

Epitope and functional classification of human neutralizing antibodies against SFTSV Gn

spinqualitylabelsall models 21au, resolution 2.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 21au 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 2.69Å Ligands: BMA, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Severe fever with thrombocytopenia syndrome virus (SFTSV) is a lethal bunyavirus lacking approved countermeasures. From SFTS survivors, we isolate 84 human monoclonal antibodies (mAbs) against the viral glycoproteins Gn and Gc. Gn-specific mAbs demonstrate superior neutralization breadth and potency compared to the restricted neutralizing activity observed with Gc. Using a high-throughput yeast display deep mutational scanning (DMS) platform, we classify Gn-head mAbs into eight epitope groups, among which four groups (IA, ID, IIIA, and IIIB) confer neutralization. Notably, mAbs BD70-4003 (group IA) and BD70-4017 (group IIIA) exhibit broad neutralization and provide 100% protection in a lethal mouse model. Cryo-electron microscopy (cryo-EM) structural analysis of these mAbs in complex with the Gn head reveals their binding interfaces, directly validating the epitope residues identified by DMS. Our study delineates the antigenic landscape of SFTSV Gn, identifies potent therapeutic candidates, and establishes DMS coupled with structural validation as a powerful framework for antibody discovery against bunyaviruses. Human monoclonal antibodies that target the SFTSV glycoprotein Gn head from four neutralizing epitope groups.,Wang Q, Li H, Jian F, Han A, Liu Y, Liu J, Yu Y, Wang J, Yu L, Wang Y, Sun H, Ma M, Shao F, Zhu L, Liu W, Cao Y Cell Rep. 2026 Apr 8;45(4):117248. doi: 10.1016/j.celrep.2026.117248. PMID:41955097 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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