7M8L
EBOV GP bound to rEBOV-442 and rEBOV-515 Fabs
Summary for 7M8L
| Entry DOI | 10.2210/pdb7m8l/pdb |
| EMDB information | 23719 |
| Descriptor | Virion spike glycoprotein 1, rEBOV-442 Fab heavy chain, rEBOV-442 Fab light chain, ... (9 entities in total) |
| Functional Keywords | ebolavirus, ebov, antibody, antibody therapeutic, mabs, filovirus, viral protein, viral protein-immune system complex, viral protein/immune system |
| Biological source | Ebola virus More |
| Total number of polymer chains | 18 |
| Total formula weight | 468888.36 |
| Authors | Murin, C.D.,Ward, A.B. (deposition date: 2021-03-30, release date: 2021-11-10, Last modification date: 2024-11-20) |
| Primary citation | Gilchuk, P.,Murin, C.D.,Cross, R.W.,Ilinykh, P.A.,Huang, K.,Kuzmina, N.,Borisevich, V.,Agans, K.N.,Geisbert, J.B.,Zost, S.J.,Nargi, R.S.,Sutton, R.E.,Suryadevara, N.,Bombardi, R.G.,Carnahan, R.H.,Bukreyev, A.,Geisbert, T.W.,Ward, A.B.,Crowe Jr., J.E. Pan-ebolavirus protective therapy by two multifunctional human antibodies. Cell, 184:5593-5607.e18, 2021 Cited by PubMed Abstract: Ebolaviruses cause a severe and often fatal illness with the potential for global spread. Monoclonal antibody-based treatments that have become available recently have a narrow therapeutic spectrum and are ineffective against ebolaviruses other than Ebola virus (EBOV), including medically important Bundibugyo (BDBV) and Sudan (SUDV) viruses. Here, we report the development of a therapeutic cocktail comprising two broadly neutralizing human antibodies, rEBOV-515 and rEBOV-442, that recognize non-overlapping sites on the ebolavirus glycoprotein (GP). Antibodies in the cocktail exhibited synergistic neutralizing activity, resisted viral escape, and possessed differing requirements for their Fc-regions for optimal in vivo activities. The cocktail protected non-human primates from ebolavirus disease caused by EBOV, BDBV, or SUDV with high therapeutic effectiveness. High-resolution structures of the cocktail antibodies in complex with GP revealed the molecular determinants for neutralization breadth and potency. This study provides advanced preclinical data to support clinical development of this cocktail for pan-ebolavirus therapy. PubMed: 34715022DOI: 10.1016/j.cell.2021.09.035 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.9 Å) |
Structure validation
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