8JJE
RBD of SARS-CoV2 spike protein with ACE2 decoy
Summary for 8JJE
| Entry DOI | 10.2210/pdb8jje/pdb |
| EMDB information | 36345 |
| Descriptor | 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) |
| Functional Keywords | sars-cov2, spike protein, ace2, ace2 decoy, viral protein, viral protein-protein binding complex, viral protein/protein binding |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 215458.99 |
| Authors | Kishikawa, J.,Hirose, M.,Kato, T.,Okamoto, T. (deposition date: 2023-05-30, release date: 2023-12-27, Last modification date: 2024-10-09) |
| Primary citation | 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 Cited by 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: 37647387DOI: 10.1126/scitranslmed.adi2623 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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