2026-01-16 九州大学
図. ヌクレオカプシドタンパク質R204P変異の解析
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1396
- https://www.kyushu-u.ac.jp/f/64456/26_0116_02.pdf
- https://www.nature.com/articles/s41467-025-67455-4
SARS-CoV-2 Omicron XECの非スパイク核カプシドR204P変異は炎症と病原性を増強する A non-spike nucleocapsid R204P mutation in SARS-CoV-2 Omicron XEC enhances inflammation and pathogenicity
Shuhei Tsujino,Masumi Tsuda,Sayaka Deguchi,Jumpei Ito,Taha Y. Taha,Hesham Nasser,Lei Wang,Julia Rosecrans,Rigel Suzuki,Saori Suzuki,Kumiko Yoshimatsu,Melanie Ott,Terumasa Ikeda,Kei Sato,Kazuo Takayama,Shinya Tanaka,Tomokazu Tamura & Takasuke FukuharaOn behalf of The Genotype to Phenotype Japan (G2P-Japan) Consortium
Nature Communications Published:14 December 2025 An unedited version of this manuscript
Abstract
The global circulation of SARS-CoV-2 in human populations has driven the emergence of Omicron subvariants, which have become highly diversified through recombination. In late 2024, SARS-CoV-2 Omicron XEC variant emerged from the recombination of two JN.1 progeny, KS.1.1 and KP.3.3, and became predominant worldwide. Here, we investigate virological features of the XEC variant. Epidemic dynamics modeling suggests that spike substitutions in XEC mainly contribute to its increased viral fitness. Additionally, four licensed antivirals are effective against XEC. Although the fusogenicity of XEC spike is comparable to that of the JN.1 spike, the intrinsic pathogenicity of XEC in male hamsters is significantly higher than that of JN.1. Notably, we find that the nucleocapsid R204P mutation of XEC enhances inflammation through NF-κB activation. Recent studies suggest that the evolutionary potential of spike protein is reaching its limit. Indeed, our findings highlight the critical role of non-spike mutations in the future evolution of SARS-CoV-2.
