Evidence map›Paper›PMID 32191456›Full record

ArticleJournal of medicinal chemistry2020

Validation and Characterization of Five Distinct Novel Inhibitors of Human Cytomegalovirus.

Arun Kapoor, Ayan K Ghosh, Michael Forman, Xin Hu, Wenjuan Ye, Noel Southall, Juan Marugan, Robert F Keyes, Brian C Smith, David J Meyers and 2 more

Open access · greenAbstract readValidation Study
In one paragraph

Article in Journal of medicinal chemistry, 2020. 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
1.3field-weighted citation impact, top 19% 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, 11 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

12 authors at 3 institutions in 1 country.

Arun KapoorDepartment of Pediatrics, Division of Infectious Disease, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
Ayan K GhoshDepartment of Pediatrics, Division of Infectious Disease, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
Michael FormanDepartment of Pathology, Johns Hopkins University, Baltimore, Maryland 21287, United States.
Xin HuNational Center for Advancing Translational Sciences (NCATS), National Institute of Health, Bethesda, Maryland 20850, United States.
Wenjuan YeNational Center for Advancing Translational Sciences (NCATS), National Institute of Health, Bethesda, Maryland 20850, United States.
Noel SouthallNational Center for Advancing Translational Sciences (NCATS), National Institute of Health, Bethesda, Maryland 20850, United States.
Juan MaruganNational Center for Advancing Translational Sciences (NCATS), National Institute of Health, Bethesda, Maryland 20850, United States.
Robert F KeyesDepartment of Biochemistry, Program in Chemical Biology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.
Brian C SmithDepartment of Biochemistry, Program in Chemical Biology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.ORCID 0000-0001-6330-2768
David J MeyersDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
Marc FerrerNational Center for Advancing Translational Sciences (NCATS), National Institute of Health, Bethesda, Maryland 20850, United States.
Ravit Arav-BogerDepartment of Pediatrics, Division of Infectious Disease, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States.ORCID 0000-0002-5363-167X
National Center for Advancing Translational Sciences · USMedical College of Wisconsin · USJohns Hopkins University · US

Funding

Discovering and Exploiting Selectivity within Tandem BromodomainsR35GM128840 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI Brian Christopher Smith · 2018 to 2026
$2.7M
High Throughput Screening for Identification of Human Cytomegalovirus InhibitorsR01DC013550 · NIDCD · MEDICAL COLLEGE OF WISCONSIN · PI BOGER, RAVIT · 2014 to 2016
$913k
NIDCD NIH HHS R01 DC013550NIGMS NIH HHS R35 GM128840
6 · The paper itself

Abstract

The critical consequences of human cytomegalovirus (HCMV) infection in the transplant population and in congenitally infected infants, the limited treatment options for HCMV, and the rise of resistant mutants toward existing therapies has fueled the search for new anti-HCMV agents. A pp28-luciferase recombinant HCMV was used as a reporter system for high-throughput screening of HCMV inhibitors. Approximately 400 000 compounds from existing libraries were screened. Subsequent validation assays using resynthesized compounds, several virus strains, and detailed virology assays resulted in the identification of five structurally unique and selective HCMV inhibitors, active at sub to low micromolar concentrations. Further characterization revealed that each compound inhibited a specific stage of HCMV replication. One compound was also active against herpes simplex virus (HSV1 and HSV2), and another compound was active against Epstein-Barr virus (EBV). Drug combination studies revealed that all five compounds were additive with ganciclovir or letermovir. Future studies will focus on optimization of these new anti-HCMV compounds along with mechanistic studies.

Indexed as

AnimalsAntiviral AgentsCells, CulturedCytomegalovirusCytomegalovirus InfectionsDose-Response Relationship, DrugDrug DiscoveryFibroblastsHumansMaleMiceAntiviral Agents

Identifiers

PMID32191456
PMCPMC7386824
OpenAlexW3012542441

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.