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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; Al-Omari, Awad; Salih, Samer; Shamsan, Abbas; Al Mutair, Abbas; Taha, Jumana; Alahmadi, Abdulaziz; Khotani, Nashwa; Alhamss, Abdelrahman; Mahmoud, Ahmed; Alquthami, Khaled; Dageeg, Abdullah; Khogeer, Asim; Hashem, Anwar M; Moraga, Paula; Volz, Eric; Almontashiri, Naif; Pain, Arnab
Nature communications, 02/2022, Letnik: 13, Številka: 1Journal Article
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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Vir: Osebne bibliografije
in: SICRIS
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