Evidence map›Paper›PMID 26079681›Full record

ArticleAntiviral research2015

Broad-spectrum non-nucleoside inhibitors of human herpesviruses.

Lora McClain, Yun Zhi, Hoyee Cheng, Ayantika Ghosh, Paolo Piazza, Michael B Yee, Santosh Kumar, Jadranka Milosevic, David C Bloom, Ravit Arav-Boger and 4 more

Open access · greenAbstract read
In one paragraph

Article in Antiviral research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.0field-weighted citation impact, top 14% 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, 20 citations in OpenAlex.

  1. Review
  2. Using 2D and 3D pluripotent stem cell models to study neurotropic viruses.Frontiers in virology (Lausanne, Switzerland) · 2022
    Article
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  11. Antiviral activity of cationic amphiphilic drugs.Expert review of anti-infective therapy · 2017
    Review
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 4 institutions in 2 countries.

Lora McClainDepartment of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Yun ZhiDepartment of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Hoyee ChengDepartment of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ayantika GhoshDepartment of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Paolo PiazzaDepartment of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.
Michael B YeeDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Santosh KumarDepartment of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jadranka MilosevicDivision of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
David C BloomDepartment of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.
Ravit Arav-BogerDepartment of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Paul R KinchingtonDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Molecular Genetics & Biochemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Robert YolkenStanley Division of Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Vishwajit NimgaonkarDepartment of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Leonardo D'AiutoDepartment of Psychiatry, WPIC, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: daiutol@upmc.edu.
University of Pittsburgh · USJohns Hopkins Medicine · USFlorida College · USTsinghua University · CN

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ethan A Rossi · 1989 to 2026
$17.8M
NEUROBEHAVIORAL STUDY OF SCHIZOPHRENIAR01MH042191 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GUR, RAQUEL E · 1987 to 2018
$7.1M
A Neurobehavioral Family Study of SchizophreniaR01MH063480 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NIMGAONKAR, VISHWAJIT LAXMIKANT · 2001 to 2018
$6.1M
Novel Artemisinin Derivatives for Cytomegalovirus TherapyR01AI093701 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BOGER, RAVIT · 2011 to 2015
$2.0M
High Throughput Screening for Identification of Human Cytomegalovirus InhibitorsR01DC013550 · NIDCD · MEDICAL COLLEGE OF WISCONSIN · PI BOGER, RAVIT · 2014 to 2016
$913k
NEI NIH HHS EY08098NEI NIH HHS P30 EY008098NIAID NIH HHS 5R01AI093701NIAID NIH HHS R01 AI093701NIDCD NIH HHS R01 DC013550NIMH NIH HHS MH63480NIMH NIH HHS R01 MH042191
6 · The paper itself

Abstract

Herpesvirus infections cause considerable morbidity and mortality through lifelong recurrent cycles of lytic and latent infection in several tissues, including the human nervous system. Acyclovir (ACV) and its prodrug, the current antivirals of choice for herpes simplex virus (HSV) and, to some extent, varicella zoster virus (VZV) infections are nucleoside analogues that inhibit viral DNA replication. Rising viral resistance and the need for more effective second-line drugs have motivated searches for additional antiviral agents, particularly non-nucleoside based agents. We evaluated the antiviral activity of five compounds with predicted lysosomotropic activity using conventional and human induced pluripotent stem cell-derived neuronal (iPSC-neurons) cultures. Their potency and toxicity were compared with ACV and the lysosomotropic agents chloroquine and bafilomycin A1. Out of five compounds tested, micromolar concentrations of 30N12, 16F19, and 4F17 showed antiviral activity comparable to ACV (50μM) during lytic herpes simplex virus type 1 (HSV-1) infections, reduced viral DNA copy number, and reduced selected HSV-1 protein levels. These compounds also inhibited the reactivation of 'quiescent' HSV-1 infection established in iPSC-neurons, but did not inhibit viral entry into host cells. The same compounds had greater potency than ACV against lytic VZV infection; they also inhibited replication of human cytomegalovirus. The anti-herpetic effects of these non-nucleoside agents merit further evaluation in vivo.

Indexed as

AnimalsAntiviral AgentsCells, CulturedCell SurvivalChlorocebus aethiopsHerpesviridaeHumansMicrobial Sensitivity TestsNeuronsAntiviral AgentsAntiviralHerpes simplex virus type 1HSVHuman cytomegalovirusInduced pluripotent stem cellsVaricella zoster virus

Identifiers

PMID26079681
PMCPMC4536133
OpenAlexW658741028

What OpenQuestion holds

Textmetadata
LicenceTDM
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.