Dataset Information

SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.

ABSTRACT: 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.

SUBMITTER: Mourier T

PROVIDER: S-EPMC8807822 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.

Mourier Tobias T Shuaib Muhammad M Hala Sharif S Mfarrej Sara S Alofi Fadwa F Naeem Raeece R Alsomali Afrah A Jorgensen David D Subudhi Amit Kumar AK Ben Rached Fathia F Guan Qingtian Q Salunke Rahul P RP Ooi Amanda A Esau Luke L Douvropoulou Olga O Nugmanova Raushan R Perumal Sadhasivam S Zhang Huoming H Rajan Issaac I Al-Omari Awad A Salih Samer S Shamsan Abbas A Al Mutair Abbas A Taha Jumana J Alahmadi Abdulaziz A Khotani Nashwa N Alhamss Abdelrahman A Mahmoud Ahmed A Alquthami Khaled K Dageeg Abdullah A Khogeer Asim A Hashem Anwar M AM Moraga Paula P Volz Eric E Almontashiri Naif N Pain Arnab A

Nature communications 20220201 1

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 inte ...[more]

PMID: 35105893

Similar Datasets

Project description:BackgroundCYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG). This study was undertaken to identify mutations in CYP1B1 in the Western region of Saudi Arabia.MethodsBlood of patients who had typical findings of PCG, were screened by direct sequencing of all coding exons and splice junctions of the CYP1B1 gene.Results34 patients were studied; 18 patients belonged to 8 families, and 16 patients were non-familial, isolated PCG. Consanguinity was found in 27/34 (79.4%) of cases. All patients were diagnosed to have bilateral PCG at birth except one child, who had glaucoma in the right eye. More males (61.8%) were affected than females (38.2%). 79.4% (27/34) of patients were solved with pathogenic mutations and 20.6% (7/34) remained unsolved. Of the solved ones, 22.2% (6/27) of patients carry a pathogenic allele on one allele while the other allele remained yet to be determined. Direct sequencing of exon 2 revealed two pathogenic variants (p.Gly61Glu, p.Glu229Lys). P.Gly61Glu substitution was found both homozygously in 63% (17/27) of cases, and heterozygously in one patient. P.Glu229Lys variant was found heterozygous in 3.7% (1/27) of cases. One pathogenic variant (p.Arg469Trp) was found in exon 3, and is present homozygously in 14.8% (4/27) of cases while four patients have this variant heterozygously. All mutations were reported previously in the Saudi population, except p.Glu229Lys. Severe cases were associated with p.Gly61Glu, and p.Arg469Trp in 50% and 30% of ten patients respectively.ConclusionsThis study confirms that CYP1B1 mutations are the most frequent cause of PCG in the Saudi population, with p.Gly61Glu being the major disease-associated mutation. P.Glu229Lys is a newly discovered mutation in our PCG patients. Patient lacking mutation in CYP1B1 gene seems likely, to have another genetic loci involved in the pathogenesis of the disease, and need further study. Genetic studies of recessive diseases such as PCG is important in consanguineous populations, since it will increase awareness and allows genetic counseling to be offered to patients and their relatives. This will not only reduce the disease to be inherited to future generations, but will also reduce the disease burden in the community.

Dataset Information

SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.

Publications

SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets