Evidence map›Paper›PMID 37896789›Full record

ArticleViruses2023

Novel Potent Autophagy Inhibitor Ka-003 Inhibits Dengue Virus Replication.

Jitra Limthongkul, Kornkamon Akkarasereenon, Tanpitcha Yodweerapong, Poramate Songthammawat, Pirut Tong-Ngam, Alisa Tubsuwan, Nawapol Kunkaew, Phongthon Kanjanasirirat, Tanawadee Khumpanied, Warawuth Wannalo and 4 more

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.6field-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

6 citing papers in PubMed, 9 citations in OpenAlex.

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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

14 authors at 2 institutions in 1 country.

Jitra LimthongkulDepartment of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Kornkamon AkkarasereenonLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.
Tanpitcha YodweerapongDepartment of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Poramate SongthammawatLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.ORCID 0000-0001-7907-1925
Pirut Tong-NgamInstitute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand.
Alisa TubsuwanInstitute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand.
Nawapol KunkaewMahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Phongthon KanjanasiriratExcellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.ORCID 0000-0002-1046-7152
Tanawadee KhumpaniedExcellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Warawuth WannaloExcellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Sukathida UbolDepartment of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Suparerk BorwornpinyoExcellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Poonsakdi PloypradithLaboratory of Medicinal Chemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.ORCID 0000-0003-2893-1598
Marisa PonpuakDepartment of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Mahidol University · THChulabhorn Research Institute · TH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Every year, dengue virus (DENV) affects millions of people. Currently, there are no approved drugs for the treatment of DENV infection. Autophagy is a conserved degradation process that was shown to be induced by DENV infection and required for optimal DENV replication. The modulation of autophagy is, therefore, considered an attractive target to treat DENV infection. This study carried out a high-content image screen analysis using Crispr-Cas9 GFP-LC3 knocked-in HeLa cells of a compound library synthesized from or inspired by natural products and their biocongener precursors to discover novel autophagy inhibitors. The screen identified Ka-003 as the most effective compound for decreasing the number of autophagic vacuoles inside cells upon autophagy induction. Ka-003 could inhibit autophagy in a dose-dependent manner at low micromolar concentrations. More importantly, Ka-003 demonstrated the concentration-dependent inhibition of DENV production in Crispr-Cas9 GFP-LC3 knocked-in THP-1 monocytes. The core structure of Ka-003, which is a methyl cyclohexene derivative, resembles those found in mulberry plants, and could be synthetically prepared in a bioinspired fashion. Taken together, data indicate that Ka-003 hampered autophagy and limited DENV replication. The low cytotoxicity of Ka-003 suggests its therapeutic potential, which warrants further studies for the lead optimization of the compound for dengue treatment.

Indexed as

DengueDengue VirusAutophagyHeLa CellsHumansVirus Replicationautophagydengue virusdrug discoverymethyl cyclohexenemulberry

Identifiers

PMID37896789
PMCPMC10611120
OpenAlexW4387137489

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.