Evidence map›Paper›PMID 24305957›Full record

ArticleJournal of laboratory automation2014

Development of a Novel Screening Strategy Designed to Discover a New Class of HIV Drugs.

Nancy Cheng, Sook-Kyung Lee, P Scott Donover, Mel Reichman, Celia A Schiffer, Emily A Hull-Ryde, Ronald Swanstrom, William P Janzen

Open access · hybridAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of laboratory automation, 2014. 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
0.7field-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, 7 citations in OpenAlex.

  1. New targets for HIV drug discovery.Drug discovery today · 2019
    Review
  2. Article
  3. Pharmacological intervention of HIV-1 maturation.Acta pharmaceutica Sinica. B · 2015
    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

8 authors at 3 institutions in 1 country.

Nancy ChengCenter for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA.
Sook-Kyung LeeDepartment of Biochemistry and Biophysics, and the UNC Center for AIDS Research, University of North Carolina at Chapel Hill, NC, USA.
P Scott DonoverLIMR Chemical Genomics Center, Inc., Lankenau Institute for Medical Research, Wynnewood, PA, USA.
Mel ReichmanLIMR Chemical Genomics Center, Inc., Lankenau Institute for Medical Research, Wynnewood, PA, USA.
Celia A SchifferDepartment of Biochemistry and Molecular Pharmacology, University of Massachusetts, Worcester, MA, USA.
Emily A Hull-RydeCenter for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA.
Ronald SwanstromDepartment of Biochemistry and Biophysics, and the UNC Center for AIDS Research, University of North Carolina at Chapel Hill, NC, USA Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC, USA.
William P JanzenCenter for Integrative Chemical Biology and Drug Discovery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC, USA Cancer Genetics Program, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA bjanzen@email.unc.edu.
University of North Carolina at Chapel Hill · USLankenau Institute for Medical Research · USUniversity of Massachusetts Chan Medical School · US

Funding

Tracking the evolution of drug resistance for highly potent HIV protease inhibitoP01GM109767 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SCHIFFER, CELIA A. · 2014 to 2018
$8.0M
High Throughput Screen For HIV-1 MA/CA Processing Site InhibitorsR21NS073052 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JANZEN, WILLIAM PERRY, SWANSTROM, RONALD I · 2011 to 2011
$148k
NIGMS NIH HHS P01 GM109767NINDS NIH HHS R21 NS073052
6 · The paper itself

Abstract

Current antiretroviral treatments target multiple pathways important for human immunodeficiency virus (HIV) multiplication, including viral entry, synthesis and integration of the DNA provirus, and the processing of viral polyprotein precursors. However, HIV is becoming increasingly resistant to these "combination therapies." Recent findings show that inhibition of HIV Gag protein cleavage into its two structural proteins, matrix (MA) and capsid (CA), has a devastating effect on viral production, revealing a potential new target class for HIV treatment. Unlike the widely used HIV protease inhibitors, this new class of inhibitor would target the substrate, not the protease enzyme itself. This approach offers a distinct advantage in that inhibitors of MA/CA would only need to affect a subset of the Gag molecules to disable viral replication. To discover MA/CA-specific inhibitors, we constructed a modified MA/CA fusion peptide (MA/CAΔ) that contains the HIV protease (PR) cleavage site as well as a tetracysteine motif for fluorescent labeling. The HIV PR cleavage of MA/CAΔ can then be monitored via fluorescence polarization (FP). We have adapted this FP assay for high-throughput screening and validated it according to industry standards using a 384-well plate format. We have currently tested 24,000 compounds in this assay and here detail the screening methodology and the results of this screening campaign.

Indexed as

High-Throughput Screening AssaysRoboticsAmino Acid MotifsAnti-HIV AgentsDrug DiscoveryFluorescence PolarizationFluorescent Dyesgag Gene Products, Human Immunodeficiency VirusHIV ProteaseHumansOligopeptidesPeptide FragmentsProteolysisRecombinant Fusion ProteinsRecombinant ProteinsReproducibility of ResultsAnti-HIV AgentsFluorescent Dyesgag Gene Products, Human Immunodeficiency VirusHIV ProteaseHIV protease substrate 1Oligopeptidesp16 protease, Human immunodeficiency virus 1Peptide FragmentsRecombinant Fusion ProteinsRecombinant ProteinsSmall Molecule LibrariesFlAsHfluorescent polarizationHIV proteaseHTSorthogonally pooled chemical library

Identifiers

PMID24305957
PMCPMC4216240
OpenAlexW2096710282

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.