1. SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.
- Author
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Mourier, Tobias, Shuaib, Muhammad, Hala, Sharif, Mfarrej, Sara, Alofi, Fadwa, Naeem, Raeece, Alsomali, Afrah, Jorgensen, David, Subudhi, Amit Kumar, Ben Rached, Fathia, Guan, Qingtian, Salunke, Rahul P., Ooi, Amanda, Esau, Luke, Douvropoulou, Olga, Nugmanova, Raushan, Perumal, Sadhasivam, Zhang, Huoming, Rajan, Issaac, and Al-Omari, Awad
- Subjects
VIRAL load ,SARS-CoV-2 ,MUTANT proteins ,COVID-19 ,GENETIC mutation ,RNA synthesis - 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. In this study, the authors sequence 892 SARS-CoV-2 genomes from Saudi Arabia and describe population dynamics and importations into the country. They identify a nucleocapsid protein mutation associated with increased viral load and host interactions and characterise its role through biochemical analyses. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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