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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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Title: SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load
Authors: Mourier, Tobias Browse this author
Shuaib, Muhammad Browse this author
Hala, Sharif Browse this author
Mfarrej, Sara Browse this author
Alofi, Fadwa Browse this author
Naeem, Raeece Browse this author
Alsomali, Afrah Browse this author
Jorgensen, David Browse this author
Subudhi, Amit Kumar Browse this author
Ben Rached, Fathia Browse this author
Guan, Qingtian Browse this author
Salunke, Rahul P. Browse this author
Ooi, Amanda Browse this author
Esau, Luke Browse this author
Douvropoulou, Olga Browse this author
Nugmanova, Raushan Browse this author
Perumal, Sadhasivam Browse this author
Zhang, Huoming Browse this author
Rajan, Issaac Browse this author
Al-Omari, Awad Browse this author
Salih, Samer Browse this author
Shamsan, Abbas Browse this author
Al Mutair, Abbas Browse this author
Taha, Jumana Browse this author
Alahmadi, Abdulaziz Browse this author
Khotani, Nashwa Browse this author
Alhamss, Abdelrahman Browse this author
Mahmoud, Ahmed Browse this author
Alquthami, Khaled Browse this author
Dageeg, Abdullah Browse this author
Khogeer, Asim Browse this author
Hashem, Anwar M. Browse this author
Moraga, Paula Browse this author
Volz, Eric Browse this author
Almontashiri, Naif Browse this author
Pain, Arnab Browse this author
Issue Date: 1-Feb-2022
Publisher: Nature Portfolio
Journal Title: Nature communications
Volume: 13
Issue: 1
Start Page: 601
Publisher DOI: 10.1038/s41467-022-28287-8
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.
Type: article
URI: http://hdl.handle.net/2115/84334
Appears in Collections:人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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