Evidence map›Paper›PMID 40510117›Full record

ArticleiScience2025

Targeting G9a-m

Adil Muneer, Ling Xie, Xuping Xie, Feng Zhang, John A Wrobel, Yan Xiong, Xufen Yu, Charles Wang, Ciprian Gheorghe, Ping Wu and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Adil MuneerDepartment of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Ling XieDepartment of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Xuping XieDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Feng ZhangDepartment of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
John A WrobelDepartment of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yan XiongMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences, and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Xufen YuMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences, and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Charles WangCenter for Genomics, Division of Microbiology & Molecular Genetics, Department of Basic Sciences, Lawrence D Longo MD Center for Perinatal Biology, Department of Gynecology and Obstetrics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
Ciprian GheorgheCenter for Genomics, Division of Microbiology & Molecular Genetics, Department of Basic Sciences, Lawrence D Longo MD Center for Perinatal Biology, Department of Gynecology and Obstetrics, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
Ping WuDepartment of Neuroscience, Cell Biology, and Anatomy, Center for Addiction Sciences and Therapeutics, Brain Health Institute, Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX, USA.
Juan SongDepartment of Pharmacology, and Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Guo-Li MingDepartment of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences, and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hongjun SongDepartment of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
Pei-Yong ShiDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Xian ChenDepartment of Biochemistry & Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Funding

Epigenetic Therapy and Prader-Willi SyndromeR01HD088626 · NICHD · YALE UNIVERSITY · PI JIANG, YONG-HUI, JIN, JIAN · 2017 to 2021
$2.8M
Novel Inhibitors of Lysine Methyltransferases G9a and GLP for the Treatment of Alzheimer's DiseaseR01AG084184 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Jian Jin · 2023 to 2026
$2.6M
NIA NIH HHS R01 AG084184NICHD NIH HHS R01 HD088626
6 · The paper itself

Abstract

N6-methyladenosine (m6A) modification pathway is hijacked by several RNA viruses, including SARS-CoV-2, making it an attractive host-directed target for development of broad-spectrum antivirals. Here, we show that histone methyltransferase G9a, through its interaction with METTL3, regulates SARS-CoV-2-mediated rewiring of host m6A methylome to ultimately promote turnover, abundance, secretion and/or phosphorylation of various viral receptors and proteases, transcription factors, cytokines/chemokines, coagulation and angiogenesis associated proteins, and fibrosis markers. More importantly, drugs targeting G9a and its associated protein EZH2 are potent inhibitors of SARS-CoV-2 replication and reverse multi-omic effects of coronavirus infection in human alveolar epithelial cells (A549-hACE2) and COVID-19 patient peripheral blood mononuclear cells (PBMCs)-with similar changes seen in multiorgan autopsy samples from COVID-19 patients. Altogether, we extend G9a function(s) beyond transcription to translational regulation during COVID-19 pathogenesis and show that targeting this master regulatory complex represents a new strategy (drug-class) that can be leveraged to combat emerging anti-viral resistance and infections.

Indexed as

Biological sciencesMicrobiologyNatural sciencesVirology

Identifiers

PMID40510117
PMCPMC12159498

What OpenQuestion 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 OpenQuestion graph.