Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A non-spike nucleocapsid R204P mutation in SARS-CoV-2 Omicron XEC enhances inflammation and pathogenicity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月14日

查看全文
  • 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 Fukuhara,
  • Hirofumi Sawa,
  • Keita Matsuno,
  • Yuma Ohari,
  • Keita Mizuma,
  • Jingshu Li,
  • Yume Mimura,
  • Naganori Nao,
  • Yoshitaka Oda,
  • Kenji Shishido,
  • Hayato Ito,
  • Naoko Misawa,
  • Keiya Uriu,
  • Shusuke Kawakubo,
  • Spyros Lytras,
  • Arnon Plianchaisuk,
  • Ziyi Guo,
  • Alfredo Hinay Jr.,
  • Wilaiporn Saikruang,
  • Kaoru Usui,
  • Luca Nishimura,
  • Yusuke Kosugi,
  • Shigeru Fujita,
  • Jarel M. Tolentino,
  • Luo Chen,
  • Lin Pan,
  • Mai Suganami,
  • Mika Chiba,
  • Kyoko Yasuda,
  • Kazuhisa Yoshimura,
  • Kenji Sadamasu,
  • Mami Nagashima,
  • Hiroyuki Asakura,
  • Isao Yoshida,
  • So Nakagawa,
  • Akifumi Takaori-Kondo,
  • Kotaro Shirakawa,
  • Rina Hashimoto,
  • Yukio Watanabe,
  • Yoshitaka Nakata,
  • Hiroki Futatsusako,
  • Ayaka Sakamoto,
  • Naoko Yasuhara,
  • Takao Hashiguchi,
  • Tateki Suzuki,
  • Kanako Kimura,
  • Yukari Nakajima,
  • Hisano Yajima,
  • Takashi Irie,
  • Ryoko Kawabata,
  • Begum MST Monira,
  • Ryo Shimizu,
  • Michael Jonathan,
  • Takamasa Ueno,
  • Chihiro Motozono,
  • Mako Toyoda,
  • Akatsuki Saito,
  • Anon Kosaka,
  • Miki Kawano

摘要

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.