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Basic Characteristics of Mutations
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Mutation Site
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R203K |
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Mutation Site Sentence
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We show that two consecutive mutations (R203K/G204R) in the nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. |
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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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N |
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Standardized Encoding Gene
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N
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Genotype/Subtype
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20A;20B;20C |
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Viral Reference
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NC_045512.2
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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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Saudi Arabia |
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Literature Information
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PMID
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35105893
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Title
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SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load
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Author
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Mourier T,Shuaib M,Hala S,Mfarrej S,Alofi F,Naeem R,Alsomali A,Jorgensen D,Subudhi AK,Ben Rached F,Guan Q,Salunke RP,Ooi A,Esau L,Douvropoulou O,Nugmanova R,Perumal S,Zhang H,Rajan I,Al-Omari A,Salih S,Shamsan A,Al Mutair A,Taha J,Alahmadi A,Khotani N,Alhamss A,Mahmoud A,Alquthami K,Dageeg A,Khogeer A,Hashem AM,Moraga P,Volz E,Almontashiri N,Pain A
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Journal
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Nature communications
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Journal Info
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2022 Feb 1;13(1):601
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Abstract
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Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. We show that two consecutive mutations (R203K/G204R) in the nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found increased interaction of GSK3A kinase simultaneously with hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein. Furthermore, the host cell transcriptome analysis suggests that the mutant N protein produces dysregulated interferon response genes. Here, we provide crucial information in linking the R203K/G204R mutations in the N protein to modulations of host-virus interactions and underline the potential of the nucleocapsid protein as a drug target during infection.
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Sequence Data
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PRJEB45515
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