9B9E
Prefusion F glycoprotein ectodomain of Nipah virus ectodomain in complex with DS90 nanobody
Summary for 9B9E
| Entry DOI | 10.2210/pdb9b9e/pdb |
| EMDB information | 44380 |
| Descriptor | Fusion glycoprotein F0, DS90 nanobody, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | f ectodomain, prefusion, viral protein, nipah virus |
| Biological source | Henipavirus nipahense More |
| Total number of polymer chains | 6 |
| Total formula weight | 193773.59 |
| Authors | Low, Y.S.,Isaacs, A.,Modhiran, N.,Watterson, D. (deposition date: 2024-04-01, release date: 2025-06-04, Last modification date: 2025-12-24) |
| Primary citation | Isaacs, A.,Nieto, G.V.,Zhang, X.,Modhiran, N.,Barr, J.,Thakur, N.,Low, Y.S.,Parry, R.H.,Barnes, J.B.,Jara, R.,Himelreichs, J.,Yao, Y.,Deride, C.,Barthou-Gatica, B.,Salinas-Rebolledo, C.,Ehrenfeld, P.,Hen, J.J.,Hayes, N.,Paramitha, D.,Morgan, M.S.,McMillan, C.L.D.,Jones, M.L.,Munro, T.P.,Khromykh, A.A.,Reading, P.C.,Young, P.R.,Chappell, K.J.,Shi, Y.,Bailey, D.,Marsh, G.A.,Chiu, S.,Rojas-Fernandez, A.,Watterson, D. A nanobody-based therapeutic targeting Nipah virus limits viral escape. Nat.Struct.Mol.Biol., 32:1920-1931, 2025 Cited by PubMed Abstract: Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an anti-fusion glycoprotein nanobody with an anti-receptor-binding glycoprotein (RBP) antibody to deliver a dual-targeting biologic that is resistant to viral escape. We show that the nanobody, DS90, engages a unique, conserved site within the fusion glycoprotein of NiV and HeV and provides neutralization and complete protection from NiV disease. Bispecific engineering of DS90 with the anti-RBP monoclonal antibody m102.4 results in neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. These findings carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants. PubMed: 40629166DOI: 10.1038/s41594-025-01598-2 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.66 Å) |
Structure validation
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