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Basic Characteristics of Mutations
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Mutation Site
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E484C |
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Mutation Site Sentence
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We observed that five mutations with high delta binding free energy agreed with ES, including E484R (delta binding free energy = 1.36 kcal/mol; ES = 0.28), E484K (delta binding free energy = 1.05 kcal/mol; ES = 0.29), E486P (delta binding free energy = 0.88 kcal/mol; ES = 0.27), E484C (delta binding free energy = 0.75 kcal/mol; ES = 0.27), and E484A (delta binding free energy = 0.74 kcal/mol; ES = 0.26) (Fig. 2C; Additional file 1: Table S1; Additional file 2: Fig. S1). |
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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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-
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Functional Impact and Mechanisms
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Disease
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-
|
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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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37596329
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Title
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In silico prediction of immune-escaping hot spots for future COVID-19 vaccine design
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Author
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Huang SH,Chen YT,Lin XY,Ly YY,Lien ST,Chen PH,Wang CT,Wu SC,Chen CC,Lin CY
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Journal
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Scientific reports
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Journal Info
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2023 Aug 18;13(1):13468
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Abstract
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The COVID-19 pandemic has had a widespread impact on a global scale, and the evolution of considerable dominants has already taken place. Some variants contained certain key mutations located on the receptor binding domain (RBD) of spike protein, such as E484K and N501Y. It is increasingly worrying that these variants could impair the efficacy of current vaccines or therapies. Therefore, analyzing and predicting the high-risk mutations of SARS-CoV-2 spike glycoprotein is crucial to design future vaccines against the different variants. In this work, we proposed an in silico approach, immune-escaping score (IES), to predict high-risk immune-escaping hot spots on the receptor-binding domain (RBD), implemented through integrated delta binding free energy measured by computational mutagenesis of spike-antibody complexes and mutation frequency calculated from viral genome sequencing data. We identified 23 potentially immune-escaping mutations on the RBD by using IES, nine of which occurred in omicron variants (R346K, K417N, N440K, L452Q, L452R, S477N, T478K, F490S, and N501Y), despite our dataset being curated before the omicron first appeared. The highest immune-escaping score (IES = 1) was found for E484K, which agrees with recent studies stating that the mutation significantly reduced the efficacy of neutralization antibodies. Furthermore, our predicted delta binding free energy and IES show a high correlation with high-throughput deep mutational scanning data (Pearson's r = 0.70) and experimentally measured neutralization titers data (mean Pearson's r = -0.80). In summary, our work presents a new method to identify the potentially immune-escaping mutations on the RBD and provides valuable insights into future COVID-19 vaccine design.
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Sequence Data
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-
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