8jje
From Proteopedia
RBD of SARS-CoV2 spike protein with ACE2 decoy
Structural highlights
FunctionACE2_HUMAN Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.[1] [2] [3] Publication Abstract from PubMedThe 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. An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models.,Urano E, Itoh Y, Suzuki T, Sasaki T, Kishikawa JI, 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 Sci Transl Med. 2023 Aug 30;15(711):eadi2623. doi: 10.1126/scitranslmed.adi2623. , Epub 2023 Aug 30. PMID:37647387[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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