7X92

The SARS-CoV-2 receptor binding domain bound with the Fab fragment of a human neutralizing antibody Ab445

7X92 の概要

• エントリーDOI: 10.2210/pdb7x92/pdb
• EMDBエントリー: 33064
• 分子名称: Spike glycoprotein, Ab445 heavy chain, Ab445 light chain, ... (4 entities in total)
• 機能のキーワード: severe acute respiratory syndrome coronavirus-2 (sars-cov-2) spike trimer, covid-19, human neutralizing antibody, rbd, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 197327.85

構造登録者

Kamada, K.,Shirouzu, M. (登録日: 2022-03-15, 公開日: 2022-12-07, 最終更新日: 2024-11-06)

主引用文献

Takeshita, M.,Fukuyama, H.,Kamada, K.,Matsumoto, T.,Makino-Okamura, C.,Uchikubo-Kamo, T.,Tomabechi, Y.,Hanada, K.,Moriyama, S.,Takahashi, Y.,Ishigaki, H.,Nakayama, M.,Nguyen, C.T.,Kitagawa, Y.,Itoh, Y.,Imai, M.,Maemura, T.,Furusawa, Y.,Ueki, H.,Iwatsuki-Horimoto, K.,Ito, M.,Yamayoshi, S.,Kawaoka, Y.,Shirouzu, M.,Ishii, M.,Saya, H.,Kondo, Y.,Kaneko, Y.,Suzuki, K.,Fukunaga, K.,Takeuchi, T.
Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models.
Iscience, 25:105596-105596, 2022

PubMed Abstract: The use of therapeutic neutralizing antibodies against SARS-CoV-2 infection has been highly effective. However, there remain few practical antibodies against viruses that are acquiring mutations. In this study, we created 494 monoclonal antibodies from patients with COVID-19-convalescent, and identified antibodies that exhibited the comparable neutralizing ability to clinically used antibodies in the neutralization assay using pseudovirus and authentic virus including variants of concerns. These antibodies have different profiles against various mutations, which were confirmed by cell-based assay and cryo-electron microscopy. To prevent antibody-dependent enhancement, N297A modification was introduced. Our antibodies showed a reduction of lung viral RNAs by therapeutic administration in a hamster model. In addition, an antibody cocktail consisting of three antibodies was also administered therapeutically to a macaque model, which resulted in reduced viral titers of swabs and lungs and reduced lung tissue damage scores. These results showed that our antibodies have sufficient antiviral activity as therapeutic candidates.

PubMed: 36406861
DOI: 10.1016/j.isci.2022.105596

実験手法

ELECTRON MICROSCOPY (4.1 Å)