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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