Evidence map›Paper›PMID 27013001›Full record

ArticleInternational journal of antimicrobial agents2016

Allosteric heat shock protein 70 inhibitors block hepatitis C virus assembly.

Ronik Khachatoorian, Rana Riahi, Ekambaram Ganapathy, Hao Shao, Nicole M Wheatley, Christopher Sundberg, Chun-Ling Jung, Piotr Ruchala, Asim Dasgupta, Vaithilingaraja Arumugaswami and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of antimicrobial agents, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 30 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.

Ronik KhachatoorianDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Rana RiahiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Ekambaram GanapathyDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Hao ShaoDepartment of Pharmaceutical Chemistry, Institute for Neurodegenerative Diseases, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Nicole M WheatleyDoe Institute for Genomics and Proteomics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Christopher SundbergDepartment of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Chun-Ling JungDepartment of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Piotr RuchalaDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Asim DasguptaDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA; UCLA AIDS Institute, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Vaithilingaraja ArumugaswamiDepartment of Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Surgery, The Board of Governors Regenerative Medicine Institute at Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Jason E GestwickiDepartment of Pharmaceutical Chemistry, Institute for Neurodegenerative Diseases, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Samuel W FrenchDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA; UCLA AIDS Institute, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Electronic address: SFrench@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of California, San Francisco · USCedars-Sinai Medical Center · US

Funding

Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Molecular Chaperones and Small MoleculesR01NS059690 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jason E Gestwicki · 2008 to 2026
$7.9M
Heat Shock Protein Synthesis Inhibitor Treatment of Hepatitis C Viral InfectionR01DK090794 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FRENCH, SAMUEL WHEELER · 2011 to 2015
$1.7M
The role of hepatitis C virus 5' untranslated region in virus morphogenesisR21AI084090 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DASGUPTA, ASIM · 2010 to 2011
$411k
NIAID NIH HHS R21 AI084090NIAID NIH HHS R21AI084090NIDDK NIH HHS P30 DK041301NIDDK NIH HHS R01 DK090794NIDDK NIH HHS R01DK090794NINDS NIH HHS NS059690NINDS NIH HHS R01 NS059690
6 · The paper itself

Abstract

The human molecular chaperones heat shock protein 70 (Hsp70) and heat shock cognate protein 70 (Hsc70) bind to the hepatitis C viral nonstructural protein 5A (NS5A) and regulate its activity. Specifically, Hsp70 is involved in NS5A-augmented internal ribosomal entry site (IRES)-mediated translation of the viral genome, whilst Hsc70 appears to be primarily important for intracellular infectious virion assembly. To better understand the importance of these two chaperones in the viral life cycle, infected human cells were treated with allosteric Hsp70/Hsc70 inhibitors (AHIs). Treatment with AHIs significantly reduced the production of intracellular virus at concentrations that were non-toxic to human hepatoma Huh7.5 cells. The supernatant of treated cultures was then used to infect naïve cells, revealing that AHIs also lowered levels of secreted virus. In contrast to their effects on virion assembly, AHIs did not impact the stability of NS5A or viral protein translation in IRES assays. These results suggest that Hsc70 plays a particularly important and sensitive role in virion assembly. Indeed, it was found that combination of AHIs with a peptide-based viral translation inhibitor exhibited additive antiviral activity. Together these results suggest that the host Hsc70 is a new antiviral target and that its inhibitors utilise a new mechanism of action.

Indexed as

Antiviral AgentsCell LineCell SurvivalEnzyme InhibitorsHepacivirusHepatocytesHSC70 Heat-Shock ProteinsHSP70 Heat-Shock ProteinsHumansVirus AssemblyAntiviral AgentsEnzyme InhibitorsHSC70 Heat-Shock ProteinsHSP70 Heat-Shock ProteinsAllosteric heat shock protein inhibitorsHepatitis C virusHsc70Hsp70Viral assemblyViral translation

Identifiers

PMID27013001
PMCPMC4833571
OpenAlexW2290533065

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.