21AV

Epitope and functional classification of human neutralizing antibodies against SFTSV Gn

Summary for 21AV

• Entry DOI: 10.2210/pdb21av/pdb
• EMDB information: 67541
• Descriptor: BD70-4017 heavy chain, BD70-4017 light chain, Envelopment polyprotein, ... (7 entities in total)
• Functional Keywords: sftsv, complex, viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 5
• Total formula weight: 87340.41

Authors

Wang, Q.R.,Jian, F.C.,Wang, Y.X. (deposition date: 2025-12-05, release date: 2026-04-29)

Primary citation

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.
Human monoclonal antibodies that target the SFTSV glycoprotein Gn head from four neutralizing epitope groups.
Cell Rep, 45:117248-117248, 2026

PubMed Abstract: 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.

PubMed: 41955097
DOI: 10.1016/j.celrep.2026.117248

Experimental method

ELECTRON MICROSCOPY (2.69 Å)