7M8L

EBOV GP bound to rEBOV-442 and rEBOV-515 Fabs

7M8L の概要

• エントリーDOI: 10.2210/pdb7m8l/pdb
• EMDBエントリー: 23719
• 分子名称: Virion spike glycoprotein 1, rEBOV-442 Fab heavy chain, rEBOV-442 Fab light chain, ... (9 entities in total)
• 機能のキーワード: ebolavirus, ebov, antibody, antibody therapeutic, mabs, filovirus, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Ebola virus; 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 468888.36

構造登録者

Murin, C.D.,Ward, A.B. (登録日: 2021-03-30, 公開日: 2021-11-10, 最終更新日: 2024-11-20)

主引用文献

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

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: 34715022
DOI: 10.1016/j.cell.2021.09.035

実験手法

ELECTRON MICROSCOPY (3.9 Å)