Evidence map›Paper›PMID 31782368›Full record

ArticleCurrent HIV research2019

Development of A Fission Yeast Cell-Based Platform for High Throughput Screening of HIV-1 Protease Inhibitors.

Zsigmond Benko, Jiantao Zhang, Richard Y Zhao

Open access · greenAbstract read
In one paragraph

Article in Current HIV research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

5 citing papers in PubMed, 6 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

3 authors at 1 institution in 1 country.

Zsigmond BenkoDepartment of Pathology, University of Maryland Medical School, Baltimore, MD 21201, United States.
Jiantao ZhangDepartment of Pathology, University of Maryland Medical School, Baltimore, MD 21201, United States.
Richard Y ZhaoDepartment of Pathology, University of Maryland Medical School, Baltimore, MD 21201, United States.
University of Maryland, Baltimore · US

Funding

A Novel and High Throughput System for Drug Discovery and Testing on Multidrug Resistant HIV-1 ProteasesR01GM127212 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI ZHAO, RICHARD YUQI · 2017 to 2018
$603k
A Novel and High Throughput System for Drug Discovery and Testing on Multidrug Resistant HIV-1 ProteasesR01AI150459 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI ZHAO, RICHARD YUQI · 2019 to 2019
$301k
NIAID NIH HHS R01 AI150459NIGMS NIH HHS R01 GM127212
6 · The paper itself

Abstract

backgroundHIV-1 protease inhibitor (PI) is one of the most potent classes of drugs in combinational antiretroviral therapies (cART). When a PI is used in combination with other anti- HIV drugs, cART can often suppress HIV-1 below detection thus prolonging the patient's lives. However, the challenge often faced by patients is the emergence of HIV-1 drug resistance. Thus, PIs with high genetic-barrier to drug-resistance are needed.

objectiveThe objective of this study was to develop a novel and simple fission yeast (Schizosaccharomyces pombe) cell-based system that is suitable for high throughput screening (HTS) of small molecules against HIV-1 protease (PR).

methodsA fission yeast RE294-GFP strain that stably expresses HIV-1 PR and green fluorescence protein (GFP) under the control of an inducible nmt1 promoter was used. Production of HIV-1 PR induces cellular growth arrest, which was used as the primary endpoint for the search of PIs and was quantified by an absorbance-based method. Levels of GFP production were used as a counter-screen control to eliminate potential transcriptional nmt1 inhibitors.

resultsBoth the absorbance-based HIV-1 PR assay and the GFP-based fluorescence assay were miniaturized and optimized for HTS. A pilot study was performed using a small drug library mixed with known PI drugs and nmt1 inhibitors. With empirically adjusted and clearly defined double-selection criteria, we were able to correctly identify the PIs and to exclude all hidden nmt1 inhibitors.

conclusionWe have successfully developed and validated a fission yeast cell-based HTS platform for the future screening and testing of HIV-1 PR inhibitors.

Indexed as

High-Throughput Screening AssaysData Interpretation, StatisticalDrug Evaluation, PreclinicalGene ExpressionGenes, ReporterHIV ProteaseHIV Protease InhibitorsHumansRecombinant Fusion ProteinsReproducibility of ResultsSchizosaccharomycesHIV ProteaseHIV Protease InhibitorsRecombinant Fusion Proteinsatazanavir (ATV)fission yeast (Schizosaccharomyces pombe)green fluorescence protein (GFP)high throughput screening (HTS)HIV-1 protease inhibitor (PI)HIV-1 protease (PR)transcriptional nmt1 inhibitor (TNI).

Identifiers

PMID31782368
PMCPMC9648856
OpenAlexW2991129609

What OpenQuestion holds

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Registered trials

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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.