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SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load

Author

Listed:
  • Tobias Mourier

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Muhammad Shuaib

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Sharif Hala

    (Infectious Disease Research Department, King Abdullah International Medical Research Centre, Ministry of National Guard Health Affairs
    King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs)

  • Sara Mfarrej

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Fadwa Alofi

    (King Fahad Hospital)

  • Raeece Naeem

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Afrah Alsomali

    (King Abdullah Medical Complex)

  • David Jorgensen

    (Imperial College, Norfolk Place, St Mary’s Campus)

  • Amit Kumar Subudhi

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Fathia Ben Rached

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Qingtian Guan

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Rahul P. Salunke

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Amanda Ooi

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Luke Esau

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Olga Douvropoulou

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Raushan Nugmanova

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Sadhasivam Perumal

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Huoming Zhang

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Issaac Rajan

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE))

  • Awad Al-Omari

    (Dr. Suliman Al-Habib Medical Group)

  • Samer Salih

    (Dr. Suliman Al-Habib Medical Group)

  • Abbas Shamsan

    (Dr. Suliman Al-Habib Medical Group)

  • Abbas Al Mutair

    (Dr. Suliman Al-Habib Medical Group)

  • Jumana Taha

    (King Faisal Specialist Hospital and Research Center)

  • Abdulaziz Alahmadi

    (Ministry of National Guard - Health Affairs)

  • Nashwa Khotani

    (Al Noor Specialist Hospital Makkah)

  • Abdelrahman Alhamss

    (King Abdul Aziz Hospital Makkah)

  • Ahmed Mahmoud

    (College of Applied Medical Sciences, Taibah University)

  • Khaled Alquthami

    (Al Noor Specialist Hospital Makkah)

  • Abdullah Dageeg

    (King Abdulaziz University Jeddah)

  • Asim Khogeer

    (General Directorate of Health Affairs Makkah Region)

  • Anwar M. Hashem

    (Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University
    King Abdulaziz University)

  • Paula Moraga

    (King Abdullah University of Science and Technology (KAUST), Computer, Electrical and Mathematical Science and Engineering Division (CEMSE))

  • Eric Volz

    (Imperial College, Norfolk Place, St Mary’s Campus)

  • Naif Almontashiri

    (College of Applied Medical Sciences, Taibah University
    Center for Genetics and Inherited Diseases, Taibah University)

  • Arnab Pain

    (King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE)
    Research Center for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University)

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.

Suggested Citation

  • Tobias Mourier & Muhammad Shuaib & Sharif Hala & Sara Mfarrej & Fadwa Alofi & Raeece Naeem & Afrah Alsomali & David Jorgensen & Amit Kumar Subudhi & Fathia Ben Rached & Qingtian Guan & Rahul P. Salunk, 2022. "SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28287-8
    DOI: 10.1038/s41467-022-28287-8
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    Cited by:

    1. Karthikeyan Dhamotharan & Sophie M. Korn & Anna Wacker & Matthias A. Becker & Sebastian Günther & Harald Schwalbe & Andreas Schlundt, 2024. "A core network in the SARS-CoV-2 nucleocapsid NTD mediates structural integrity and selective RNA-binding," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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