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: COVID-19; R203K/G204R; SARS-CoV-2; fatality; fitness; infectivity; mutation; nucleocapsid; virulence.
【저자키워드】 COVID-19, SARS-CoV-2, Mutation, Infectivity, nucleocapsid, fitness, virulence, R203K/G204R, fatality, 【초록키워드】 pandemic, Mutation, adaptive, hamsters, variant, COVID-19 severity, variants of concern, Transmission, in silico, virus, variants, Spike protein, nucleocapsid protein, Protein, Phylogenetic analysis, Viral, SARS-CoV-2 variants, B.1.1.7, nucleocapsid, fitness, experiment, virulence, association, fatality, Combination, Frequency, replication advantage, human lung cells, positive, SARS-CoV-2 nucleocapsid, competition, SARS-CoV-2 lineage, observé, addition, contribute, the spike protein, analyses, human lung cell, the SARS-CoV-2,