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.

Details

Title
SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load
Author
Mourier Tobias 1   VIAFID ORCID Logo  ; Shuaib Muhammad 1   VIAFID ORCID Logo  ; Sharif, Hala 2 ; Mfarrej Sara 1   VIAFID ORCID Logo  ; Alofi Fadwa 3 ; Raeece, Naeem 1   VIAFID ORCID Logo  ; Alsomali Afrah 4 ; Jorgensen, David 5 ; Subudhi, Amit Kumar 1   VIAFID ORCID Logo  ; Ben Rached Fathia 1   VIAFID ORCID Logo  ; Guan Qingtian 1 ; Salunke, Rahul P 1 ; Ooi, Amanda 1 ; Esau, Luke 1 ; Douvropoulou Olga 1 ; Nugmanova Raushan 1 ; Sadhasivam, Perumal 1 ; Zhang Huoming 1   VIAFID ORCID Logo  ; Rajan Issaac 1 ; Al-Omari, Awad 6 ; Salih Samer 6 ; Abbas, Shamsan 6 ; Abbas, Al Mutair 6 ; Taha Jumana 7 ; Alahmadi Abdulaziz 8 ; Khotani Nashwa 9 ; Abdelrahman, Alhamss 10 ; Ahmed, Mahmoud 11   VIAFID ORCID Logo  ; Alquthami Khaled 12 ; Dageeg Abdullah 13 ; Khogeer Asim 14 ; Hashem, Anwar M 15   VIAFID ORCID Logo  ; Moraga, Paula 16 ; Volz, Eric 5   VIAFID ORCID Logo  ; Almontashiri Naif 17 ; Pain Arnab 18   VIAFID ORCID Logo 

 King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE), Thuwal-Jeddah, Saudi Arabia (GRID:grid.45672.32) (ISNI:0000 0001 1926 5090) 
 Infectious Disease Research Department, King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia (GRID:grid.452607.2) (ISNI:0000 0004 0580 0891); King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia (GRID:grid.452607.2) 
 King Fahad Hospital, Infectious Diseases Department, Madinah, Saudi Arabia (GRID:grid.45672.32) 
 King Abdullah Medical Complex, Infectious Diseases Department, Jeddah, Saudi Arabia (GRID:grid.45672.32) 
 Imperial College, Norfolk Place, St Mary’s Campus, School of Public Health, Faculty of Medicine, London, United Kingdom (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111) 
 Dr. Suliman Al-Habib Medical Group, Riyadh, Saudi Arabia (GRID:grid.45672.32) 
 King Faisal Specialist Hospital and Research Center, Department of Neuroscience, Riyadh, Saudi Arabia (GRID:grid.415310.2) (ISNI:0000 0001 2191 4301) 
 Ministry of National Guard - Health Affairs, Department of Preventive Medicine, Riyadh, Saudi Arabia (GRID:grid.416641.0) (ISNI:0000 0004 0607 2419) 
 Al Noor Specialist Hospital Makkah, Infectious Diseases Medical Department, Makkah, Saudi Arabia (GRID:grid.416641.0) 
10  King Abdul Aziz Hospital Makkah, Gastroenterology Department, Makkah, Saudi Arabia (GRID:grid.415252.5) 
11  College of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia (GRID:grid.412892.4) (ISNI:0000 0004 1754 9358) 
12  Al Noor Specialist Hospital Makkah, Infectious Diseases Medical Department, Makkah, Saudi Arabia (GRID:grid.412892.4) 
13  King Abdulaziz University Jeddah, Department of Medicine, Jeddah, Saudi Arabia (GRID:grid.412125.1) (ISNI:0000 0001 0619 1117) 
14  General Directorate of Health Affairs Makkah Region, Plan and Research Department, Makkah, Saudi Arabia (GRID:grid.412125.1) 
15  Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia (GRID:grid.412125.1) (ISNI:0000 0001 0619 1117); King Abdulaziz University, Department of Medical Microbiology and Parasitology, Faculty of Medicine, Jeddah, Saudi Arabia (GRID:grid.412125.1) (ISNI:0000 0001 0619 1117) 
16  King Abdullah University of Science and Technology (KAUST), Computer, Electrical and Mathematical Science and Engineering Division (CEMSE), Thuwal-Jeddah, Saudi Arabia (GRID:grid.45672.32) (ISNI:0000 0001 1926 5090) 
17  College of Applied Medical Sciences, Taibah University, Madinah, Saudi Arabia (GRID:grid.412892.4) (ISNI:0000 0004 1754 9358); Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunwarah, Saudi Arabia (GRID:grid.412892.4) (ISNI:0000 0004 1754 9358) 
18  King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE), Thuwal-Jeddah, Saudi Arabia (GRID:grid.45672.32) (ISNI:0000 0001 1926 5090); Research Center for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan (GRID:grid.39158.36) (ISNI:0000 0001 2173 7691) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2624599668
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.