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.
Artículo
en Inglés
| 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.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Genoma Viral
/
Mutación Missense
/
Proteínas de la Nucleocápside de Coronavirus
/
SARS-CoV-2
/
COVID-19
Tipo de estudio:
Ensayo controlado aleatorizado
Límite:
Humanos
País/Región como asunto:
Asia
Idioma:
Inglés
Revista:
Nat Commun
Asunto de la revista:
Biologia
/
Ciencia
Año:
2022
Tipo del documento:
Artículo
País de afiliación:
S41467-022-28287-8
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