Evidence map›Paper›PMID 36975214›Full record

ArticleAntimicrobial agents and chemotherapy2023

The Natural Stilbenoid (-)-Hopeaphenol Inhibits HIV Transcription by Targeting Both PKC and NF-κB Signaling and Cyclin-Dependent Kinase 9.

Ian Tietjen, Cole Schonhofer, Amanda Sciorillo, Maya E Naidu, Zahra Haq, Toshitha Kannan, Andrew V Kossenkov, Jocelyn Rivera-Ortiz, Karam Mounzer, Colin Hart and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 32% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Phytochemical Investigation ofMolecules (Basel, Switzerland) · 2024
    Article
  3. Journal of experimental pharmacology · 2024
    Article
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 5 institutions in 4 countries.

Ian TietjenThe Wistar Institute, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-8991-6490
Cole SchonhoferFaculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Amanda SciorilloThe Wistar Institute, Philadelphia, Pennsylvania, USA.
Maya E NaiduFaculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Zahra HaqFaculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Toshitha KannanThe Wistar Institute, Philadelphia, Pennsylvania, USA.
Andrew V KossenkovThe Wistar Institute, Philadelphia, Pennsylvania, USA.
Jocelyn Rivera-OrtizThe Wistar Institute, Philadelphia, Pennsylvania, USA.
Karam MounzerJonathan Lax Immune Disorders Treatment Center, Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, Pennsylvania, USA.
Colin HartThe Wistar Institute, Philadelphia, Pennsylvania, USA.
Kwasi GyampohThe Wistar Institute, Philadelphia, Pennsylvania, USA.
Zhe YuanThe Wistar Institute, Philadelphia, Pennsylvania, USA.
Karren D BeattieGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, Queensland, Australia.
Topul RaliSchool of Natural and Physical Sciences, The University of Papua New Guinea, Port Moresby, Papua New Guinea.
Kristy Shuda McGuireThe Wistar Institute, Philadelphia, Pennsylvania, USA.
Rohan A DavisGriffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, Queensland, Australia.
Luis J MontanerThe Wistar Institute, Philadelphia, Pennsylvania, USA.
The Wistar Institute · USSimon Fraser University · CAGriffith University · AUPhiladelphia Fight · USUniversity of Papua New Guinea · PG

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Ronald G Collman · 1999 to 2026
$78.6M
BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination ImmunotherapyUM1AI164570 · NIAID · WISTAR INSTITUTE · PI Luis J Montaner, James L. Riley · 2021 to 2026
$34.7M
NIAID NIH HHS P30 AI045008NIAID NIH HHS UM1 AI164570Wellcome TrustWellcome Trust 107752/Z/15/Z
6 · The paper itself

Abstract

Despite effective combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to harbor replication-competent and transcriptionally active virus in infected cells, which in turn can lead to ongoing viral antigen production, chronic inflammation, and increased risk of age-related comorbidities. To identify new agents that may inhibit postintegration HIV beyond cART, we screened a library of 512 pure compounds derived from natural products and identified (-)-hopeaphenol as an inhibitor of HIV postintegration transcription at low to submicromolar concentrations without cytotoxicity. Using a combination of global RNA sequencing, plasmid-based reporter assays, and enzyme activity studies, we document that hopeaphenol inhibits protein kinase C (PKC)- and downstream NF-κB-dependent HIV transcription as well as a subset of PKC-dependent T-cell activation markers, including interleukin-2 (IL-2) cytokine and CD25 and HLA-DRB1 RNA production. In contrast, it does not substantially inhibit the early PKC-mediated T-cell activation marker CD69 production of IL-6 or NF-κB signaling induced by tumor necrosis factor alpha (TNF-α). We further show that hopeaphenol can inhibit cyclin-dependent kinase 9 (CDK9) enzymatic activity required for HIV transcription. Finally, it inhibits HIV replication in peripheral blood mononuclear cells (PBMCs) infected

Indexed as

HIV InfectionsStilbenesCyclin-Dependent Kinase 9HumansLeukocytes, MononuclearNF-kappa BPhenolsProtein Kinase CRNAVirus LatencyVirus ReplicationCyclin-Dependent Kinase 9hopeaphenolNF-kappa BPhenolsProtein Kinase CRNAStilbenesantiviral pharmacologycyclin kinase inhibitorshuman immunodeficiency virusnatural antimicrobial productstranscriptional regulationviral latencyviral pathogenesis

Identifiers

PMID36975214
PMCPMC10112218
OpenAlexW4361191279

What OpenQuestion 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 OpenQuestion graph.