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.

先前的研究发现，SARS-CoV-2 核衣壳 (N) 蛋白上同时发生的 R203K/G204R 突变在令人关注或感兴趣的新兴变体中的频率正在增加。通过综合计算机分析，本研究证明 R203K/G204R 具有适应性，而大规模系统发育分析表明 R203K/G204R 与高传播性 SARS-CoV-2 谱系 B.1.1.7 的出现相关。竞争实验表明，203K/204R 变体比之前的 R203/G204 变体具有复制优势，这可能与核糖核衣壳 (RNP) 组装有关。此外，203K/204R病毒在人肺细胞和仓鼠中表现出更强的感染性。因此，我们观察到 COVID-19 严重程度增加与 203K/204R 样本频率之间呈正相关。我们的工作表明，203K/204R 突变有助于增强特定 SARS-CoV-2 变体的传播和毒力。除了刺突蛋白的突变外，核衣壳蛋白的突变对于大流行期间的病毒传播也很重要。