8AWM

RVFV GnH with Fab268 bound

Summary for 8AWM

• Entry DOI: 10.2210/pdb8awm/pdb
• Descriptor: Heavy chain Fab268, Light chain Fab268, Glycoprotein (3 entities in total)
• Functional Keywords: rvfv, gn, fab268, viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 82476.57

Authors

Hulswit, R.J.G.,Bowden, T.A.,Stass, R. (deposition date: 2022-08-30, release date: 2023-09-06, Last modification date: 2024-11-13)

Primary citation

Chapman, N.S.,Hulswit, R.J.G.,Westover, J.L.B.,Stass, R.,Paesen, G.C.,Binshtein, E.,Reidy, J.X.,Engdahl, T.B.,Handal, L.S.,Flores, A.,Gowen, B.B.,Bowden, T.A.,Crowe Jr., J.E.
Multifunctional human monoclonal antibody combination mediates protection against Rift Valley fever virus at low doses.
Nat Commun, 14:5650-5650, 2023

PubMed Abstract: The zoonotic Rift Valley fever virus (RVFV) can cause severe disease in humans and has pandemic potential, yet no approved vaccine or therapy exists. Here we describe a dual-mechanism human monoclonal antibody (mAb) combination against RVFV that is effective at minimal doses in a lethal mouse model of infection. We structurally analyze and characterize the binding mode of a prototypical potent Gn domain-A-binding antibody that blocks attachment and of an antibody that inhibits infection by abrogating the fusion process as previously determined. Surprisingly, the Gn domain-A antibody does not directly block RVFV Gn interaction with the host receptor low density lipoprotein receptor-related protein 1 (LRP1) as determined by a competitive assay. This study identifies a rationally designed combination of human mAbs deserving of future investigation for use in humans against RVFV infection. Using a two-pronged mechanistic approach, we demonstrate the potent efficacy of a rationally designed combination mAb therapeutic.

PubMed: 37704627
DOI: 10.1038/s41467-023-41171-3

Experimental method

X-RAY DIFFRACTION (3.5 Å)