Evidence map›Paper›PMID 42091603›Full record

ArticleNature communications2026

MELK inhibition disrupts actin cytoskeleton and broadly restricts human coronavirus infections.

Kuai Yu, Qiaorui Yao, Dong Wang, Qingtao Hu, Dandan Li, Fang Li, Fenghua Chen, Jingyi Su, Ting Huang, Qing Zhang and 9 more

Abstract read
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In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

19 authors.

Kuai Yu *State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Qiaorui Yao *State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Dong Wang *State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Qingtao Hu *State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.ORCID http://orcid.org/0000-0002-8291-7116
Dandan Li *State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Fang LiState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Fenghua ChenState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Jingyi SuState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Ting HuangState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Qing ZhangProteomics and Metabolomics Core Facility, Guangzhou National Laboratory, Guangzhou, China.
Zishuo LinSchool of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
Wei RanState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.ORCID http://orcid.org/0009-0002-2269-4026
Yiliang WangState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Yuzheng ZhouInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Shuai WenState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Yuting LinState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Yaming JiuUnit of Cell Biology and Imaging Study of Pathogen Host Interaction, Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai, China. ymjiu@siii.cas.cn.ORCID http://orcid.org/0000-0002-8601-8820
Jingxian ZhaoState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. zhaojingxian@gird.cn.ORCID http://orcid.org/0000-0002-2615-3182
Jincun ZhaoState Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, National Centre for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. zhaojincun@gird.cn.ORCID http://orcid.org/0000-0003-2515-5589

Funding

China Postdoctoral Science Foundation 2021M700944National Natural Science Foundation of China (National Science Foundation of China) 32222022National Natural Science Foundation of China (National Science Foundation of China) 82025001, 82495200, 82495203National Natural Science Foundation of China (National Science Foundation of China) 82301981National Natural Science Foundation of China (National Science Foundation of China) 82402053National Natural Science Foundation of China (National Science Foundation of China) 82495200
6 · The paper itself

Abstract

Protein kinases regulate numerous critical biological processes in eukaryotic cells and are important targets for drug development. However, the common functional protein kinases and corresponding inhibitors with broad-spectrum therapeutic potential for human coronavirus infections remain largely unknown. By integrating global phosphoproteomics and high-content screening, we identify maternal embryonic leucine zipper kinase (MELK) as a common kinase required for the infections of multiple human coronaviruses currently circulating in the population. Inhibition of MELK activity by OTSSP167, or genetic depletion of its expression, exhibits broad antiviral effects in cells, human airway organoids as well as in mice under a prophylactic setting. Intriguingly, super-resolution imaging reveals that MELK colocalizes with the cellular actin cytoskeleton that is required for viral infection. Subsequently, live-cell imaging demonstrates that OTSSP167 treatment disrupts the dynamics of actin cytoskeleton. Mechanistic analysis reveals that MELK directly phosphorylates a key actin-depolymerizing protein, cofilin-1 at S3 and T70, thereby suppressing its actin-severing activity. Inhibiting MELK activity or expression activates cofilin-1 and disrupts actin filament formation, thereby impeding multiple steps of viral life cycle. Collectively, our study reveals a common regulation of coronavirus infections by MELK through modulation of actin cytoskeleton, and the broad antiviral effect of OTSSP167 as a novel actin cytoskeleton modulator.

Indexed as

Actin CytoskeletonCoronavirus InfectionsProtein Kinase InhibitorsProtein Serine-Threonine KinasesAnimalsAntiviral AgentsCofilin 1CoronavirusHumansMicePhosphorylationAntiviral AgentsCofilin 1MELK protein, humanProtein Kinase InhibitorsProtein Serine-Threonine Kinases

Identifiers

PMID42091603
PMCPMC13358123

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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.