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Basic Characteristics of Mutations
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Mutation Site
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L452R |
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Mutation Site Sentence
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The results showed that neither the L452R nor N501Y single mutation affected the inhibitory activity of NT-108, while the single amino acid mutation, E484K, completely lost the inhibitory activity. |
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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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RBD |
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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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Functional Impact and Mechanisms
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Disease
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COVID-19
|
|
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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Treatment
|
- |
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Location
|
- |
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Literature Information
|
|
PMID
|
40121330
|
|
Title
|
Structural and virological identification of neutralizing antibody footprint provides insights into therapeutic antibody design against SARS-CoV-2 variants
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Author
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Anraku Y,Kita S,Onodera T,Sato A,Tadokoro T,Ito S,Adachi Y,Kotaki R,Suzuki T,Sasaki J,Shiwa-Sudo N,Iwata-Yoshikawa N,Nagata N,Kobayashi S,Kazuki Y,Oshimura M,Nomura T,Sasaki M,Orba Y,Suzuki T,Sawa H,Hashiguchi T,Fukuhara H,Takahashi Y,Maenaka K
|
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Journal
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Communications biology
|
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Journal Info
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2025 Mar 22;8(1):483
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Abstract
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Medical treatments using potent neutralizing SARS-CoV-2 antibodies have achieved remarkable improvements in clinical symptoms, changing the situation for the severity of COVID-19 patients. We previously reported an antibody, NT-108 with potent neutralizing activity. However, the structural and functional basis for the neutralizing activity of NT-108 has not yet been understood. Here, we demonstrated the therapeutic effects of NT-108 in a hamster model and its protective effects at low doses. Furthermore, we determined the cryo-EM structure of NT-108 in complex with SARS-CoV-2 spike. The single-chain Fv construction of NT-108 improved the cryo-EM maps because of the prevention of preferred orientations induced by Fab orientation. The footprints of NT-108 illuminated how escape mutations such as E484K evade from class 2 antibody recognition without ACE2 affinity attenuation. The functional and structural basis for the potent neutralizing activity of NT-108 provides insights into the rational design of therapeutic antibodies.
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Sequence Data
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-
|
|
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