Evidence map›Paper›PMID 27504492›Full record

ArticleACS central science2016

Reconstitution and Functional Analysis of a Full-Length Hepatitis C Virus NS5B Polymerase on a Supported Lipid Bilayer.

Nam-Joon Cho, Edward A Pham, Rachel J Hagey, Vincent J Lévêque, Han Ma, Klaus Klumpp, Jeffrey S Glenn

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

Article in ACS central science, 2016. 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 27% 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, 9 citations in OpenAlex.

  1. A thirst for advancement.Nature materials · 2018
    Article
  2. Article
  3. Article
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

7 authors at 3 institutions in 1 country.

Nam-Joon ChoDepartment of Chemical Engineering, Stanford University, Palo Alto, California 94305, United States; Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California 94305, United States.
Edward A PhamDepartment of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California 94305, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Palo Alto, California 94305, United States.
Rachel J HageyDepartment of Microbiology and Immunology, Stanford University School of Medicine , Palo Alto, California 94305, United States.
Vincent J LévêqueVirology Discovery, Hoffmann-La Roche Inc. , Nutley, New Jersey 07110, United States.
Han MaVirology Discovery, Hoffmann-La Roche Inc. , Nutley, New Jersey 07110, United States.
Klaus KlumppVirology Discovery, Hoffmann-La Roche Inc. , Nutley, New Jersey 07110, United States.
Jeffrey S GlennDepartment of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California 94305, United States; Department of Microbiology and Immunology, Stanford University School of Medicine, Palo Alto, California 94305, United States; Veterans Administration Medical Center, Palo Alto, California 94304, United States.
La Roche College · USStanford University · USPalo Alto University · US

Funding

Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
MOLECULAR BASIS OF HOST-PARASITE INTERACTIONT32AI007328 · NIAID · STANFORD UNIVERSITY · PI JUSTIN L SONNENBURG · 1987 to 2026
$11.9M
The PIP2-virus interface and PI 4-kinase: novel biology and validation targetsR01AI099245 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2012 to 2016
$5.2M
HCV NS4B: Translating molecular virology into novel antiviral therapiesR01AI087917 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2010 to 2014
$2.0M
HCV NS5A: Molecular Virology and Antiviral TargetR01DK064223 · NIDDK · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2004 to 2010
$1.5M
Structure-function determination of the Hepatitis C Virus negative RNA strand's 3'-terminal sequenceF30DK099017 · NIDDK · STANFORD UNIVERSITY · PI PHAM, EDWARD ANHOA · 2013 to 2015
$98k
NIAID NIH HHS R01 AI087917NIAID NIH HHS R01 AI099245NIAID NIH HHS T32 AI007328NIAID NIH HHS U19 AI109662NIDDK NIH HHS F30 DK099017NIDDK NIH HHS R01 DK064223
6 · The paper itself

Abstract

Therapeutic targeting of membrane-associated viral proteins is complicated by the challenge of investigating their enzymatic activities in the native membrane-bound state. To permit functional characterization of these proteins, we hypothesized that the supported lipid bilayer (SLB) can support in situ reconstitution of membrane-associated viral protein complexes. As proof-of-principle, we selected the hepatitis C virus (HCV) NS5B polymerase which is essential for HCV genome replication, and determined that the SLB platform enables functional reconstitution of membrane protein activity. Quartz crystal microbalance with dissipation (QCM-D) monitoring enabled label-free detection of full-length NS5B membrane association, its interaction with replicase subunits NS3, NS5A, and template RNA, and most importantly its RNA synthesis activity. This latter activity could be inhibited by the addition of candidate small molecule drugs. Collectively, our results demonstrate that the SLB platform can support functional studies of membrane-associated viral proteins engaged in critical biological activities.

Identifiers

PMID27504492
PMCPMC4965852
OpenAlexW2442654775

What OpenQuestion holds

Textmetadata
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.