9L2K

The crystal structure of SFTSV Gn and SD22 antibody complex

Summary for 9L2K

• Entry DOI: 10.2210/pdb9l2k/pdb
• Descriptor: Envelopment polyprotein, SD22 heavy chain, SD22 light chain, ... (5 entities in total)
• Functional Keywords: sd22, sftsv, antibody, gn, severe fever with thrombocytopenia virus, viral protein/immune system, viral protein-immune system complex
• Biological source: Severe fever with thrombocytopenia syndrome virus (Severe fever with thrombocytopenia virus, Huaiyangshan banyangvirus); More
• Total number of polymer chains: 3
• Total formula weight: 86241.55

Authors

Shi, W.F.,Quan, C.S.,Qi, J.X. (deposition date: 2024-12-17, release date: 2025-06-18, Last modification date: 2025-12-31)

Primary citation

Quan, C.,Nie, K.,Ma, D.,Su, C.,Li, L.,Zheng, W.,Yin, C.,Wang, Y.,Yang, P.,Peng, D.,Liu, X.,Li, W.,Liu, W.,Shan, C.,Zheng, J.,Liu, D.,Zhang, H.,Carr, M.J.,Gao, G.F.,Qi, J.,Shi, W.
Molecular mechanism of potently neutralizing human monoclonal antibodies against severe fever with thrombocytopenia virus infection.
J.Virol., 99:e0053325-e0053325, 2025

PubMed Abstract: Although severe fever with thrombocytopenia syndrome (SFTS) was first described in China in 2009, the case fatality rate remains >40% among patients with multi-organ failure. To date, no antivirals specifically targeting SFTSV have been approved. We obtained several monoclonal antibodies (mAbs) from SFTS survivors by single-cell RNA-seq. Neutralization and animal experiments were applied to assess the effects of these mAbs and , and co-crystal structures with SFTSV-Gn glycoproteins were determined by X-ray crystallography. The mAbs SD4, SD12, and SD22 targeted the SFTSV-Gn with high neutralizing activities, and, remarkably, SD4 and SD22 exhibited values in the range of 32-83 pM for different viral genotypes. Notably, a single administration (20 mg/kg) of SD4 and SD22 showed 100% protection in mice at day 3 post-inoculation (dpi). Importantly, SD4 also provided 60% protection at a lower dose (0.3 mg/kg) when administered at 3 dpi. The crystallographic structures of SD4, SD22, and SD12 with Gn were determined at 3.3 Å, 2.8 Å, and 2.4 Å, respectively, which revealed that they recognized a conserved antigenic epitope around the hexon wellhead edge. These human-derived mAbs have significant therapeutic potential for severe SFTS cases and provide a basis for rational antibody-based vaccine designs and clinical trials.

PubMed: 40539781
DOI: 10.1128/jvi.00533-25

Experimental method

X-RAY DIFFRACTION (2.78 Å)