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Basic Characteristics of Mutations
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Mutation Site
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D614G |
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Mutation Site Sentence
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Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody,3E8,blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2,SARS-CoV-2 mutant variants (SARS-CoV-2-D614G,B.1.1.7,B.1.351,B.1.617.1,and P.1),SARS-CoV and HCoV-NL63,without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 ""knock-in"" mice. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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S |
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Standardized Encoding Gene
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S
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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34433803
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Title
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ACE2-targeting monoclonal antibody as potent and broad-spectrum coronavirus blocker
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Author
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Chen Y,Zhang YN,Yan R,Wang G,Zhang Y,Zhang ZR,Li Y,Ou J,Chu W,Liang Z,Wang Y,Chen YL,Chen G,Wang Q,Zhou Q,Zhang B,Wang C
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Journal
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Signal transduction and targeted therapy
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Journal Info
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2021 Aug 25;6(1):315
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Abstract
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The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 ""knock-in"" mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and ""alanine walk"" studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and ""broad-spectrum"" management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.
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Sequence Data
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-
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