Evidence map›Paper›PMID 40502047›Full record

ArticlebioRxiv : the preprint server for biology2025

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

Shuhei Tsujino, Masumi Tsuda, Jumpei Ito, Sayaka Deguchi, Taha Y Taha, Hesham Nasser, Lei Wang, Julia Rosecrans, Rigel Suzuki, Saori Suzuki and 9 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Shuhei TsujinoDepartment of Virology, Faculty of Medicine Sciences, Kyushu University, Fukuoka, Japan.ORCID 0009-0004-7542-3785
Masumi TsudaDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Jumpei ItoDivision of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Sayaka DeguchiCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Taha Y TahaGladstone Institutes, San Francisco, California, United States of America.
Hesham NasserDivision of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.
Lei WangDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Julia RosecransGladstone Institutes, San Francisco, California, United States of America.
Rigel SuzukiDepartment of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.
Saori SuzukiDepartment of Virology, Faculty of Medicine Sciences, Kyushu University, Fukuoka, Japan.
Kumiko YoshimatsuInstitute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Melanie OttGladstone Institutes, San Francisco, California, United States of America.ORCID 0000-0002-5697-1274
Genotype to Phenotype Japan (G2P-Japan) Consortium
Terumasa IkedaDivision of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.ORCID 0000-0003-2869-9450
Kazuo TakayamaCenter for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.ORCID 0000-0002-1132-2457
Kei SatoDivision of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID 0000-0003-4431-1380
Shinya TanakaDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.ORCID 0000-0001-6470-3301
Tomokazu TamuraDepartment of Virology, Faculty of Medicine Sciences, Kyushu University, Fukuoka, Japan.ORCID 0000-0003-1395-6610
Takasuke FukuharaDepartment of Virology, Faculty of Medicine Sciences, Kyushu University, Fukuoka, Japan.ORCID 0000-0001-5471-8331

Funding

RESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Melanie Maria Ott · 2018 to 2026
$21.4M
NIAID NIH HHS U19 AI135990
6 · The paper itself

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 investigated virological features of the XEC variant. Epidemic dynamics modeling suggested that spike substitutions in XEC mainly contribute to its increased viral fitness. Additionally, four licensed antivirals were effective against XEC. Although the fusogenicity of XEC spike is comparable to that of the JN.1 spike, the intrinsic pathogenicity of XEC in hamsters was significantly higher than that of JN.1. Notably, we found that the nucleocapsid R204P mutation of XEC enhanced 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.

Indexed as

COVID-19inflammationNF-κBnucleocapsidpathogenicityR204PSARS-CoV-2XEC

Identifiers

PMID40502047
PMCPMC12154822

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.