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-Omari; Samer 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

doi:10.1038/s41467-022-28287-8

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

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.13(1), pp.601-601

01/02/2022

DOI: https://doi.org/10.1038/s41467-022-28287-8

PMID: 35105893

Abstract

Coronavirus Nucleocapsid Proteins - genetics

Coronavirus Nucleocapsid Proteins - metabolism

COVID-19 - enzymology

COVID-19 - genetics

COVID-19 - virology

Genome, Viral

Glycogen Synthase Kinase 3 - genetics

Glycogen Synthase Kinase 3 - metabolism

Host-Pathogen Interactions

Humans

Mutation, Missense

Nucleocapsid - genetics

Nucleocapsid - metabolism

Phosphorylation

Phylogeny

Protein Binding

SARS-CoV-2 - classification

SARS-CoV-2 - genetics

SARS-CoV-2 - physiology

Saudi Arabia

Viral Load

Virus Replication

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.

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Title: SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load
Creators - without role: Tobias Mourier - King Abdullah University of Science and Technology
Muhammad Shuaib - King Abdullah University of Science and Technology
Sharif Hala - King Saud bin Abdulaziz University for Health Sciences
Sara Mfarrej - King Abdullah University of Science and Technology
Fadwa Alofi - King Fahad Hospital Jeddah
Raeece Naeem - King Abdullah University of Science and Technology
Afrah Alsomali - Infectious Diseases Department, King Abdullah Medical Complex, Jeddah, Saudi Arabia
David Jorgensen - Imperial College London
Amit Kumar Subudhi - King Abdullah University of Science and Technology
Fathia Ben Rached - King Abdullah University of Science and Technology
Qingtian Guan - King Abdullah University of Science and Technology
Rahul P Salunke - King Abdullah University of Science and Technology
Amanda Ooi - King Abdullah University of Science and Technology
Luke Esau - King Abdullah University of Science and Technology
Olga Douvropoulou - King Abdullah University of Science and Technology
Raushan Nugmanova - King Abdullah University of Science and Technology
Sadhasivam Perumal - King Abdullah University of Science and Technology
Huoming Zhang - King Abdullah University of Science and Technology
Issaac Rajan - King Abdullah University of Science and Technology
Awad Al-Omari - Dr. Suliman Al-Habib Medical Group, Riyadh, Saudi Arabia
Samer Salih - Dr. Suliman Al-Habib Medical Group, Riyadh, Saudi Arabia
Abbas Shamsan - Dr. Suliman Al-Habib Medical Group, Riyadh, Saudi Arabia
Abbas Al Mutair - Dr. Suliman Al-Habib Medical Group, Riyadh, Saudi Arabia
Jumana Taha - King Faisal Specialist Hospital & Research Centre
Abdulaziz Alahmadi - National Guard Health Affairs
Nashwa Khotani - Infectious Diseases Medical Department, Al Noor Specialist Hospital Makkah, Makkah, Saudi Arabia
Abdelrahman Alhamss - King Abdul Aziz University Hospital
Ahmed Mahmoud - Taibah University
Khaled Alquthami - Infectious Diseases Medical Department, Al Noor Specialist Hospital Makkah, Makkah, MOH, Saudi Arabia
Abdullah Dageeg - King Abdulaziz University
Asim Khogeer - Hera General Hospital
Anwar M Hashem - King Abdulaziz University
Paula Moraga - King Abdullah University of Science and Technology
Eric Volz - Faculty
Naif Almontashiri - Taibah University
Arnab Pain - King Abdullah University of Science and Technology
Publication Details: Nature communications, Vol.13(1), pp.601-601
Grant note: Rapid Research Response Team (R3T) by Vice President - Research (VPR) office in KAUST. / King Abdullah University of Science and Technology (KAUST) MR/R015600/1 / Medical Research Council KAUST faculty baseline fund (BAS/1/1020-01-01) / King Abdullah University of Science and Technology (KAUST) Proposal number: 5-20-01-002-0008 / King Abdulaziz City for Science and Technology (KACST) MC_PC_19012 / Medical Research Council
Identifiers: 9913696508331
Academic Unit: Alfaisal University; King Fahd University of Petroleum & Minerals; King Abdulaziz University; King Abdullah University of Science & Technology; Princess Nourah bint Abdulrahman University; Taibah University; King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article