SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load.
Nat Commun
; 13(1): 601, 2022 02 01.
Article
in English
| MEDLINE | ID: covidwho-1671558
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Genome, Viral
/
Mutation, Missense
/
Coronavirus Nucleocapsid Proteins
/
SARS-CoV-2
/
COVID-19
Type of study:
Randomized controlled trials
Limits:
Humans
Country/Region as subject:
Asia
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2022
Document Type:
Article
Affiliation country:
S41467-022-28287-8
Similar
MEDLINE
...
LILACS
LIS