Nucleocapsid mutations R203K/G204R increase the infectivity, fitness, and virulence of SARS-CoV-2.
Cell Host Microbe
; 29(12): 1788-1801.e6, 2021 12 08.
Article
in English
| MEDLINE | ID: covidwho-1509671
ABSTRACT
Previous work found that the co-occurring mutations R203K/G204R on the SARS-CoV-2 nucleocapsid (N) protein are increasing in frequency among emerging variants of concern or interest. Through a combination of in silico analyses, this study demonstrates that R203K/G204R are adaptive, while large-scale phylogenetic analyses indicate that R203K/G204R associate with the emergence of the high-transmissibility SARS-CoV-2 lineage B.1.1.7. Competition experiments suggest that the 203K/204R variants possess a replication advantage over the preceding R203/G204 variants, possibly related to ribonucleocapsid (RNP) assembly. Moreover, the 203K/204R virus shows increased infectivity in human lung cells and hamsters. Accordingly, we observe a positive association between increased COVID-19 severity and sample frequency of 203K/204R. Our work suggests that the 203K/204R mutations contribute to the increased transmission and virulence of select SARS-CoV-2 variants. In addition to mutations in the spike protein, mutations in the nucleocapsid protein are important for viral spreading during the pandemic.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Genome, Viral
/
Amino Acid Substitution
/
Coronavirus Nucleocapsid Proteins
/
SARS-CoV-2
/
COVID-19
/
Mutation
Type of study:
Observational study
/
Prognostic study
/
Randomized controlled trials
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Cell Host Microbe
Journal subject:
Microbiology
Year:
2021
Document Type:
Article
Affiliation country:
J.chom.2021.11.005
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