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

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. Salunke, Amanda Ooi, Luke Esau, Olga Douvropoulou, Raushan Nugmanova, Sadhasivam Perumal, Huoming Zhang, Issaac Rajan, Awad Al-OmariSamer Salih, Abbas Shamsan, Abbas Al Mutair, Jumana Taha, Abdulaziz Alahmadi, Nashwa Khotani, Abdelrahman Alhamss, Ahmed Mahmoud, Khaled Alquthami, Abdullah Dageeg, Asim Khogeer, Anwar M. Hashem, Paula Moraga, Eric Volz, Naif Almontashiri, Arnab Pain*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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.

Original languageEnglish (US)
Article number601
JournalNature Communications
Issue number1
StatePublished - Dec 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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