Evidence map›Paper›PMID 37906052›Full record

ArticleThe Journal of cell biology2023

Inhibition of lysosome-tethered Ragulator-Rag-3D complex restricts the replication of Enterovirus 71 and Coxsackie A16.

Xinhui Wang, Zhilin Hu, Wei Zhang, Shuwei Wu, Yongjin Hao, Xia Xiao, Jingjing Li, Xiaoliang Yu, Chengkui Yang, Jingfeng Wang and 7 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 10% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 1 country.

Xinhui Wang *State Key Laboratory of Common Mechanism Research for Major Diseases, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0000-0003-1732-2594
Zhilin Hu *Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.ORCID 0000-0003-0920-6219
Wei Zhang *State Key Laboratory of Common Mechanism Research for Major Diseases, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0009-0007-5738-2993
Shuwei WuJiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, China.ORCID 0009-0001-6892-0829
Yongjin HaoJiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, China.ORCID 0009-0009-1796-6462
Xia XiaoNational Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID 0000-0001-9819-5819
Jingjing LiState Key Laboratory of Common Mechanism Research for Major Diseases, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0000-0002-0047-3217
Xiaoliang YuState Key Laboratory of Common Mechanism Research for Major Diseases, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0000-0002-1117-7157
Chengkui YangState Key Laboratory of Common Mechanism Research for Major Diseases, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0000-0002-1423-5965
Jingfeng WangState Key Laboratory of Common Mechanism Research for Major Diseases, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0000-0002-5170-3887
Huiying ZhangState Key Laboratory of Common Mechanism Research for Major Diseases, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0000-0003-2112-8153
Feng MaNational Key Laboratory of Immunity and Inflammation, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0000-0002-2975-0118
Weifeng ShiDepartment of Laboratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China.ORCID 0000-0003-2737-8655
Jianwei WangNational Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID 0000-0002-1116-4559
Xiaobo LeiNational Health Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID 0000-0002-3455-6723
Xiaohu ZhangJiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, China.ORCID 0000-0002-0579-1636
Sudan HeState Key Laboratory of Common Mechanism Research for Major Diseases, and Key Laboratory of Synthetic Biology Regulatory Elements, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Suzhou, China.ORCID 0000-0002-0846-1210
Chinese Academy of Medical Sciences & Peking Union Medical College · CNSoochow University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enterovirus 71 (EV71) and Coxsackie A16 (CVA16) are two major causative agents of hand, foot, and mouth disease (HFMD) in young children. However, the mechanisms regulating the replication and pathogenesis of EV71/CVA16 remain incompletely understood. We performed a genome-wide CRISPR-Cas9 knockout screen and identified Ragulator as a mediator of EV71-induced apoptosis and pyroptosis. The Ragulator-Rag complex is required for EV71 and CVA16 replication. Upon infection, the Ragulator-Rag complex recruits viral 3D protein to the lysosomal surface through the interaction between 3D and RagB. Disruption of the lysosome-tethered Ragulator-Rag-3D complex significantly impairs the replication of EV71/CVA16. We discovered a novel EV71 inhibitor, ZHSI-1, which interacts with 3D and significantly reduces the lysosomal tethering of 3D. ZHSI-1 treatment significantly represses replication of EV71/CVA16 as well as virus-induced pyroptosis associated with viral pathogenesis. Importantly, ZHSI-1 treatment effectively protects against EV71 infection in neonatal and young mice. Thus, our study indicates that targeting lysosome-tethered Ragulator-Rag-3D may be an effective therapeutic strategy for HFMD.

Indexed as

Enterovirus A, HumanHand, Foot and Mouth DiseaseViral Nonstructural ProteinsAnimalsApoptosisCRISPR-Cas SystemsDisease Models, AnimalLysosomesMicePyroptosisVirus ReplicationViral Nonstructural Proteins

Identifiers

PMID37906052
PMCPMC10619577
OpenAlexW4388034596

What Socratic holds

Textmetadata
LicenceCC BY
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.