Advances in developing ACE2 derivatives against SARS-CoV-2

Extensive immune evasion of SARS-CoV-2 rendered therapeutic antibodies ineffective in the COVID-19 pandemic. Propagating SARS-CoV-2 variants are characterised by immune evasion capacity through key amino acid mutations, but can still bind human angiotensin-converting enzyme 2 (ACE2) through the spik...

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Published inThe Lancet. Microbe Vol. 4; no. 5; pp. e369 - e378
Main Authors Zhang, Haoran, Lv, Panjing, Jiang, Jingrui, Liu, Yahui, Yan, Ruixi, Shu, Sainan, Hu, Bing, Xiao, Han, Cai, Kun, Yuan, Shuai, Li, Yan
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.05.2023
Subjects
Angiotensin-Converting Enzyme 2 - chemistry
Angiotensin-Converting Enzyme 2 - genetics
Angiotensin-Converting Enzyme 2 - metabolism
Antibodies, Viral
COVID-19
Humans
Pandemics
Peptidyl-Dipeptidase A - chemistry
Peptidyl-Dipeptidase A - genetics
Recombinant Proteins - genetics
SARS-CoV-2
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Abstract Extensive immune evasion of SARS-CoV-2 rendered therapeutic antibodies ineffective in the COVID-19 pandemic. Propagating SARS-CoV-2 variants are characterised by immune evasion capacity through key amino acid mutations, but can still bind human angiotensin-converting enzyme 2 (ACE2) through the spike protein and are, thus, sensitive to ACE2-mimicking decoys as inhibitors. In this Review, we examine advances in the development of ACE2 derivatives from the past 3 years, including the recombinant ACE2 proteins, ACE2-loaded extracellular vesicles, ACE2-mimicking antibodies, and peptide or mini-protein mimetics of ACE2. Several ACE2 derivatives are granted potent neutralisation efficacy against SARS-CoV-2 variants that rival or surpass endogenous antibodies by various auxiliary techniques such as chemical modification and practical recombinant design. The derivatives also represent enhanced production efficiency and improved bioavailability. In addition to these derivatives of ACE2, new effective therapeutics against SARS-CoV-2 variants are expected to be developed.
AbstractList Extensive immune evasion of SARS-CoV-2 rendered therapeutic antibodies ineffective in the COVID-19 pandemic. Propagating SARS-CoV-2 variants are characterised by immune evasion capacity through key amino acid mutations, but can still bind human angiotensin-converting enzyme 2 (ACE2) through the spike protein and are, thus, sensitive to ACE2-mimicking decoys as inhibitors. In this Review, we examine advances in the development of ACE2 derivatives from the past 3 years, including the recombinant ACE2 proteins, ACE2-loaded extracellular vesicles, ACE2-mimicking antibodies, and peptide or mini-protein mimetics of ACE2. Several ACE2 derivatives are granted potent neutralisation efficacy against SARS-CoV-2 variants that rival or surpass endogenous antibodies by various auxiliary techniques such as chemical modification and practical recombinant design. The derivatives also represent enhanced production efficiency and improved bioavailability. In addition to these derivatives of ACE2, new effective therapeutics against SARS-CoV-2 variants are expected to be developed.
Author Liu, Yahui
Xiao, Han
Yan, Ruixi
Jiang, Jingrui
Zhang, Haoran
Hu, Bing
Cai, Kun
Lv, Panjing
Li, Yan
Yuan, Shuai
Shu, Sainan
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Snippet Extensive immune evasion of SARS-CoV-2 rendered therapeutic antibodies ineffective in the COVID-19 pandemic. Propagating SARS-CoV-2 variants are characterised...
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SubjectTerms Angiotensin-Converting Enzyme 2 - chemistry
Angiotensin-Converting Enzyme 2 - genetics
Angiotensin-Converting Enzyme 2 - metabolism
Antibodies, Viral
COVID-19
Humans
Pandemics
Peptidyl-Dipeptidase A - chemistry
Peptidyl-Dipeptidase A - genetics
Recombinant Proteins - genetics
SARS-CoV-2
Title Advances in developing ACE2 derivatives against SARS-CoV-2
URI https://dx.doi.org/10.1016/S2666-5247(23)00011-3
https://www.ncbi.nlm.nih.gov/pubmed/36934742
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Volume 4
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