Evidence map›Paper›PMID 34341353›Full record

ArticleNature communications2021

SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation.

Pan Pan, Miaomiao Shen, Zhenyang Yu, Weiwei Ge, Keli Chen, Mingfu Tian, Feng Xiao, Zhenwei Wang, Jun Wang, Yaling Jia and 12 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 341 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
341citing papers in PubMed, 1 pooled it
33.2field-weighted citation impact, top 1% of its field
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

341 citing papers in PubMed, 1 synthesis or guideline pooled it, 501 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Nasal administration of anti-CD3 mAb (Foralumab) downregulatesProceedings of the National Academy of Sciences of the United States of America · 2023
    Trial
  4. Review
  5. Article
  6. Inflammasomes in respiratory diseases: from disease pathogenesis to drug development and use of multi-omics.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
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  20. Article

281 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 1 country.

Pan Pan *The First Affiliated Hospital of Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-7214-1393
Miaomiao Shen *State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0002-9680-1130
Zhenyang Yu *State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0003-1776-9230
Weiwei GeState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0002-8397-7903
Keli ChenState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0002-0125-3646
Mingfu TianGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0003-0122-6397
Feng XiaoState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.ORCID http://orcid.org/0000-0002-7895-7940
Zhenwei WangGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-1627-6082
Jun WangThe Affiliated ShunDe Hospital of Jinan University, Foshan, China.ORCID http://orcid.org/0000-0003-2554-7216
Yaling JiaGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0003-0025-7271
Wenbiao WangGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0003-4944-764X
Pin WanGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0001-5374-2356
Jing ZhangGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0003-1380-3948
Weijie ChenGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-4559-6317
Zhiwei LeiGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-9406-2127
Xin ChenGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
Zhen LuoGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-1142-2845
Qiwei ZhangGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0002-2770-111X
Meng XuThe First Affiliated Hospital of Jinan University, Guangzhou, China.ORCID http://orcid.org/0000-0001-7387-0734
Geng LiGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China. lg@gzucm.edu.cn.ORCID http://orcid.org/0000-0002-2441-2427
Yongkui LiGuangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China. lyk070@jnu.edu.cn.ORCID http://orcid.org/0000-0002-1532-4855
Jianguo WuThe First Affiliated Hospital of Jinan University, Guangzhou, China. jwu898@jnu.edu.cn.ORCID http://orcid.org/0000-0002-8326-2895
Jinan University · CNWuhan University · CNFoshan University · CNFirst Affiliated Hospital of Jinan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Excessive inflammatory responses induced upon SARS-CoV-2 infection are associated with severe symptoms of COVID-19. Inflammasomes activated in response to SARS-CoV-2 infection are also associated with COVID-19 severity. Here, we show a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. N protein facilitates maturation of proinflammatory cytokines and induces proinflammatory responses in cultured cells and mice. Mechanistically, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates NLRP3 inflammasome assembly. More importantly, N protein aggravates lung injury, accelerates death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production are blocked by MCC950 (a specific inhibitor of NLRP3) and Ac-YVAD-cmk (an inhibitor of caspase-1). Therefore, this study reveals a distinct mechanism by which SARS-CoV-2 N protein promotes NLRP3 inflammasome activation and induces excessive inflammatory responses.

Indexed as

AnimalsCells, CulturedCoronavirus Nucleocapsid ProteinsCOVID-19CytokinesHEK293 CellsHumansInflammasomesInflammationLung InjuryMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinPhosphoproteinsCoronavirus Nucleocapsid ProteinsCytokinesInflammasomesNLR Family, Pyrin Domain-Containing 3 Proteinnucleocapsid phosphoprotein, SARS-CoV-2Phosphoproteins

Identifiers

PMID34341353
PMCPMC8329225
OpenAlexW3191928958

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.