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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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The SARS-CoV-2 Spike variant D614G favors an open conformational state. |
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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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33863729
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Title
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The SARS-CoV-2 Spike variant D614G favors an open conformational state
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Author
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Mansbach RA,Chakraborty S,Nguyen K,Montefiori DC,Korber B,Gnanakaran S
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Journal
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Science advances
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Journal Info
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2021 Apr 16;7(16):eabf3671
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Abstract
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The COVID-19 (coronavirus disease 2019) pandemic underwent a rapid transition with the emergence of a dominant viral variant (from the ""D-form"" to the ""G-form"") that carried an amino acid substitution D614G in its ""Spike"" protein. The G-form is more infectious in vitro and is associated with increased viral loads in the upper airways. To gain insight into the molecular-level underpinnings of these characteristics, we used microsecond all-atom simulations. We show that changes in the protein energetics favor a higher population of infection-capable states in the G-form through release of asymmetry present in the D-form inter-protomer interactions. Thus, the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor. It is also predicted to be more neutralization sensitive owing to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies. These results are critical for vaccine design.
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Sequence Data
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-
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