Evidence map›Paper›PMID 41392175›Full record

ArticleNature communications2025

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 and 9 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Shuhei Tsujino *Department of Virology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.ORCID http://orcid.org/0009-0004-7542-3785
Masumi Tsuda *Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.ORCID http://orcid.org/0000-0001-5400-5905
Sayaka Deguchi *Department of Synthetic Human Body System, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
Jumpei Ito *Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0003-0440-8321
Taha Y TahaGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7344-7490
Hesham NasserDivision of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.ORCID http://orcid.org/0000-0001-9163-1665
Lei WangDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan.ORCID http://orcid.org/0000-0001-6145-395X
Julia RosecransGladstone Institutes, San Francisco, CA, USA.
Rigel SuzukiDepartment of Virology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Saori SuzukiDepartment of Virology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kumiko YoshimatsuInstitute for Genetic Medicine, Hokkaido University, Sapporo, Japan.ORCID http://orcid.org/0000-0002-0062-2753
Melanie OttGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-5697-1274
Terumasa IkedaDivision of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.ORCID http://orcid.org/0000-0003-2869-9450
Kei SatoDivision of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0003-4431-1380
Kazuo TakayamaDepartment of Synthetic Human Body System, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan. takayama.kazuo@tmd.ac.jp.
Shinya TanakaDepartment of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan. tanaka@med.hokudai.ac.jp.ORCID http://orcid.org/0000-0001-6470-3301
Tomokazu TamuraDepartment of Virology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. tamura.tomokazu.956@m.kyushu-u.ac.jp.
Takasuke FukuharaDepartment of Virology, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan. fukuhara.takasuke.169@m.kyushu-u.ac.jp.ORCID http://orcid.org/0000-0001-5471-8331
Genotype to Phenotype Japan (G2P-Japan) Consortium

Funding

Targeting Viroporins and Coronavirus M ProteinU19AI171110 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nevan J Krogan · 2022 to 2026
$103.4M
RESEARCH PROJECT 2U19AI135990 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Melanie Maria Ott · 2018 to 2026
$21.4M
NIAID NIH HHS L70 AI172046NIAID NIH HHS U19 AI135990NIAID NIH HHS U19 AI171110
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 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.

Indexed as

Coronavirus Nucleocapsid ProteinsCOVID-19InflammationSARS-CoV-2AnimalsAntiviral AgentsCricetinaeHumansMaleMutationNF-kappa BSpike Glycoprotein, CoronavirusVirulenceAntiviral AgentsCoronavirus Nucleocapsid ProteinsNF-kappa BSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID41392175
PMCPMC12819382

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.