8K5H

Structure of the SARS-CoV-2 BA.1 spike with UT28-RD

8K5H の概要

• エントリーDOI: 10.2210/pdb8k5h/pdb
• EMDBエントリー: 36906
• 分子名称: Spike glycoprotein, UT28K-RD Fab heavy chain, UT28K-RD Fab light chain, ... (5 entities in total)
• 機能のキーワード: sars-cov-2, antibody, spike protein, structural protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV,SARS-CoV-2); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 463435.17

構造登録者

Chen, L.,Kita, S.,Anraku, Y.,Maenaka, K. (登録日: 2023-07-21, 公開日: 2023-12-27, 最終更新日: 2024-10-23)

主引用文献

Ozawa, T.,Ikeda, Y.,Chen, L.,Suzuki, R.,Hoshino, A.,Noguchi, A.,Kita, S.,Anraku, Y.,Igarashi, E.,Saga, Y.,Inasaki, N.,Taminishi, S.,Sasaki, J.,Kirita, Y.,Fukuhara, H.,Maenaka, K.,Hashiguchi, T.,Fukuhara, T.,Hirabayashi, K.,Tani, H.,Kishi, H.,Niimi, H.
Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1.
Structure, 32:263-272.e7, 2024

PubMed Abstract: SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (V T28R/N57D), UT28K-RD targeting the mutation site. In vitro and in vivo experiments demonstrated the efficacy of UT28K-RD in neutralizing Omicron BA.1. Although the experimentally determined structure partially differed from the predicted model, our study serves as a successful case of antibody design, wherein the predicted amino acid substitution enhanced the recognition of the previously elusive Omicron BA.1. We anticipate that numerous similar cases will be reported, showcasing the potential of this approach for improving protein-protein interactions. Our findings will contribute to the development of novel therapeutic strategies for highly mutable viruses, such as SARS-CoV-2.

PubMed: 38228146
DOI: 10.1016/j.str.2023.12.013

実験手法

ELECTRON MICROSCOPY (3.22 Å)