5Y0A

Cryo-EM structure of zika virus complexed with Fab of ZKA190 at pH 8.0 and 37 celsius degree

Summary for 5Y0A

• Entry DOI: 10.2210/pdb5y0a/pdb
• EMDB information: 6793
• Descriptor: protein E, variable region of Fab ZKA190 heavy chain, variable region of Fab ZKA190 light chain (3 entities in total)
• Functional Keywords: virus, antibody, complex, virus-immune system complex, icosahedral virus, virus/immune system
• Biological source: Zika virus (strain Mr 766) (ZIKV); More
• Total number of polymer chains: 9
• Total formula weight: 211245.54

Authors

Wang, J.Q.,Lok, S.M. (deposition date: 2017-07-15, release date: 2017-10-04, Last modification date: 2024-03-27)

Primary citation

Wang, J.,Bardelli, M.,Espinosa, D.A.,Pedotti, M.,Ng, T.S.,Bianchi, S.,Simonelli, L.,Lim, E.X.Y.,Foglierini, M.,Zatta, F.,Jaconi, S.,Beltramello, M.,Cameroni, E.,Fibriansah, G.,Shi, J.,Barca, T.,Pagani, I.,Rubio, A.,Broccoli, V.,Vicenzi, E.,Graham, V.,Pullan, S.,Dowall, S.,Hewson, R.,Jurt, S.,Zerbe, O.,Stettler, K.,Lanzavecchia, A.,Sallusto, F.,Cavalli, A.,Harris, E.,Lok, S.M.,Varani, L.,Corti, D.
A Human Bi-specific Antibody against Zika Virus with High Therapeutic Potential.
Cell, 171:229-241.e15, 2017

PubMed Abstract: Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature. However, ZIKV escape mutants emerged in vitro and in vivo in the presence of ZKA190, as well as of other neutralizing mAbs. To counter this problem, we developed a bispecific antibody (FIT-1) comprising ZKA190 and a second mAb specific for DII of E protein. In addition to retaining high in vitro and in vivo potencies, FIT-1 robustly prevented viral escape, warranting its development as a ZIKV immunotherapy.

PubMed: 28938115
DOI: 10.1016/j.cell.2017.09.002

Experimental method

ELECTRON MICROSCOPY (22 Å)