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

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 journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Article number	601
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-28287-8
State	Published - Dec 2022

ASJC Scopus subject areas

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

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Mourier, T., Shuaib, M., Hala, S., Mfarrej, S., Alofi, F., Naeem, R., Alsomali, A., Jorgensen, D., Subudhi, A. K., Ben Rached, F., Guan, Q., Salunke, R. P., Ooi, A., Esau, L., Douvropoulou, O., Nugmanova, R., Perumal, S., Zhang, H., Rajan, I., ... Pain, A. (2022). SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load. Nature Communications, 13(1), Article 601. https://doi.org/10.1038/s41467-022-28287-8

@article{b7c4e3276c1c4df5b603692af0f93b04,

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

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.",

author = "Tobias Mourier and Muhammad Shuaib and Sharif Hala and Sara Mfarrej and Fadwa Alofi and Raeece Naeem and Afrah Alsomali and David Jorgensen and Subudhi, {Amit Kumar} and {Ben Rached}, Fathia and Qingtian Guan and Salunke, {Rahul P.} and Amanda Ooi and Luke Esau and Olga Douvropoulou and Raushan Nugmanova and Sadhasivam Perumal and Huoming Zhang and Issaac Rajan and Awad Al-Omari and Samer Salih and Abbas Shamsan and {Al Mutair}, Abbas and Jumana Taha and Abdulaziz Alahmadi and Nashwa Khotani and Abdelrahman Alhamss and Ahmed Mahmoud and Khaled Alquthami and Abdullah Dageeg and Asim Khogeer and Hashem, {Anwar M.} and Paula Moraga and Eric Volz and Naif Almontashiri and Arnab Pain",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-28287-8",

language = "English (US)",

volume = "13",

journal = "Nature Communications",

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Mourier, T, Shuaib, M, Hala, S, Mfarrej, S, Alofi, F, Naeem, R, Alsomali, A, Jorgensen, D, Subudhi, AK, Ben Rached, F, Guan, Q, Salunke, RP, Ooi, A, Esau, L, Douvropoulou, O, Nugmanova, R, Perumal, S, Zhang, H, Rajan, I, Al-Omari, A, Salih, S, Shamsan, A, Al Mutair, A, Taha, J, Alahmadi, A, Khotani, N, Alhamss, A, Mahmoud, A, Alquthami, K, Dageeg, A, Khogeer, A, Hashem, AM, Moraga, P, Volz, E, Almontashiri, N & Pain, A 2022, 'SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load', Nature Communications, vol. 13, no. 1, 601. https://doi.org/10.1038/s41467-022-28287-8

TY - JOUR

T1 - SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load

AU - Mourier, Tobias

AU - Shuaib, Muhammad

AU - Hala, Sharif

AU - Mfarrej, Sara

AU - Alofi, Fadwa

AU - Naeem, Raeece

AU - Alsomali, Afrah

AU - Jorgensen, David

AU - Subudhi, Amit Kumar

AU - Ben Rached, Fathia

AU - Guan, Qingtian

AU - Salunke, Rahul P.

AU - Ooi, Amanda

AU - Esau, Luke

AU - Douvropoulou, Olga

AU - Nugmanova, Raushan

AU - Perumal, Sadhasivam

AU - Zhang, Huoming

AU - Rajan, Issaac

AU - Al-Omari, Awad

AU - Salih, Samer

AU - Shamsan, Abbas

AU - Al Mutair, Abbas

AU - Taha, Jumana

AU - Alahmadi, Abdulaziz

AU - Khotani, Nashwa

AU - Alhamss, Abdelrahman

AU - Mahmoud, Ahmed

AU - Alquthami, Khaled

AU - Dageeg, Abdullah

AU - Khogeer, Asim

AU - Hashem, Anwar M.

AU - Moraga, Paula

AU - Volz, Eric

AU - Almontashiri, Naif

AU - Pain, Arnab

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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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U2 - 10.1038/s41467-022-28287-8

DO - 10.1038/s41467-022-28287-8

M3 - Article

C2 - 35105893

AN - SCOPUS:85124061905

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 601

ER -

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

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