9UB6

Crystal structure of SFTSV Gn head with nanobody Nb261

Summary for 9UB6

• Entry DOI: 10.2210/pdb9ub6/pdb
• Descriptor: Glycoprotein N, Nanobody VHH261, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sftsv, viral protein
• Biological source: SFTS virus HB29; More
• Total number of polymer chains: 2
• Total formula weight: 48805.88

Authors

Wu, Y.,Chang, Z.,Wu, X. (deposition date: 2025-04-02, release date: 2025-10-22, Last modification date: 2026-05-06)

Primary citation

Wu, X.,Zhu, L.,Liang, S.,Chang, Z.,Wang, Y.,Zou, Q.,Xu, Z.,Zhang, D.,Hu, J.,Geng, S.,Li, Z.,Yu, W.,Hu, Z.,Chen, M.,Cao, K.,Jia, B.,Wei, H.,Cai, R.,Long, J.,Yang, X.,Yang, Q.,Yu, Z.,Shi, L.,Xu, B.,Zheng, Y.,Meng, S.,Cai, J.,Zhou, G.,Zhu, K.,Dou, Y.,Lou, Z.,Li, M.,Wu, Y.,Wu, Z.
A rationally designed cocktail of nanobodies elicited by heterologous vaccination confers protection against SFTSV in preclinical models.
Sci Transl Med, 17:eady9025-eady9025, 2025

PubMed Abstract: Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne phlebovirus, poses a growing public health threat, with no approved vaccines or targeted therapies. Its genetic diversity and rapid reassortment have hindered the development of broadly effective interventions. Here, we isolated and characterized broadly neutralizing camelid nanobodies generated by a heterologous immunization strategy. These nanobodies exhibited cross-subtype neutralization and conferred protection against disease in humanized and lethal murine models of SFTSV infection. Structural analysis revealed binding to distinct, nonoverlapping epitopes on the viral glycoprotein complex. A rationally designed cocktail leveraging this epitope diversity achieved complete viral inhibition through synergistic mechanisms. In both murine and immunocompetent ferret models, the cocktail enabled efficient viral clearance and full protection against lethal challenge. These results demonstrate the therapeutic potential of nanobody cocktails for SFTSV infection and establish a generalizable framework for nanobody-based countermeasures against genetically variable emerging viruses, including other members of the Bunyavirales order.

PubMed: 41259535
DOI: 10.1126/scitranslmed.ady9025

Experimental method

X-RAY DIFFRACTION (2.89 Å)