1. SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.
- Author
-
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, and Pain A
- Subjects
- COVID-19 enzymology, COVID-19 genetics, Coronavirus Nucleocapsid Proteins metabolism, Glycogen Synthase Kinase 3 genetics, Glycogen Synthase Kinase 3 metabolism, Host-Pathogen Interactions, Humans, Nucleocapsid genetics, Nucleocapsid metabolism, Phosphorylation, Phylogeny, Protein Binding, SARS-CoV-2 classification, SARS-CoV-2 physiology, Saudi Arabia, Viral Load, Virus Replication, COVID-19 virology, Coronavirus Nucleocapsid Proteins genetics, Genome, Viral, Mutation, Missense, SARS-CoV-2 genetics
- 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., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF