8JJE

RBD of SARS-CoV2 spike protein with ACE2 decoy

8JJE の概要

• エントリーDOI: 10.2210/pdb8jje/pdb
• EMDBエントリー: 36345
• 分子名称: Angiotensin-converting enzyme 2, Spike glycoprotein, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• 機能のキーワード: sars-cov2, spike protein, ace2, ace2 decoy, viral protein, viral protein-protein binding complex, viral protein/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 215458.99

構造登録者

Kishikawa, J.,Hirose, M.,Kato, T.,Okamoto, T. (登録日: 2023-05-30, 公開日: 2023-12-27, 最終更新日: 2024-10-09)

主引用文献

Urano, E.,Itoh, Y.,Suzuki, T.,Sasaki, T.,Kishikawa, J.I.,Akamatsu, K.,Higuchi, Y.,Sakai, Y.,Okamura, T.,Mitoma, S.,Sugihara, F.,Takada, A.,Kimura, M.,Nakao, S.,Hirose, M.,Sasaki, T.,Koketsu, R.,Tsuji, S.,Yanagida, S.,Shioda, T.,Hara, E.,Matoba, S.,Matsuura, Y.,Kanda, Y.,Arase, H.,Okada, M.,Takagi, J.,Kato, T.,Hoshino, A.,Yasutomi, Y.,Saito, A.,Okamoto, T.
An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models.
Sci Transl Med, 15:eadi2623-eadi2623, 2023

PubMed Abstract: The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments.

PubMed: 37647387
DOI: 10.1126/scitranslmed.adi2623

実験手法

ELECTRON MICROSCOPY (3.4 Å)