Evidence map›Paper›PMID 27539384›Full record

ArticleAntiviral research2016

High-throughput screening for the identification of small-molecule inhibitors of the flaviviral protease.

Anuradha Balasubramanian, Mark Manzano, Tadahisa Teramoto, Rajendra Pilankatta, Radhakrishnan Padmanabhan

Open access · greenAbstract read
In one paragraph

Article in Antiviral research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

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  14. Targeting the protease of West Nile virus.RSC medicinal chemistry · 2021
    Review
  15. Review
  16. Article
  17. Article
  18. Strategies Towards Protease Inhibitors for Emerging Flaviviruses.Advances in experimental medicine and biology · 2018
    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

5 authors at 1 institution in 1 country.

Anuradha BalasubramanianDepartment of Microbiology and Immunology, Georgetown University, Washington, D.C., USA.
Mark ManzanoDepartment of Microbiology and Immunology, Georgetown University, Washington, D.C., USA.
Tadahisa TeramotoDepartment of Microbiology and Immunology, Georgetown University, Washington, D.C., USA.
Rajendra PilankattaDepartment of Microbiology and Immunology, Georgetown University, Washington, D.C., USA.
Radhakrishnan PadmanabhanDepartment of Microbiology and Immunology, Georgetown University, Washington, D.C., USA. Electronic address: rp55@georgetown.edu.
Georgetown University · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SHOEMAKER, CHARLES BIX · 2003 to 2013
$113.7M
Development of Antiviral Therapeutics for Dengue: Inhibitors of Viral ProteaseU01AI082068 · NIAID · GEORGETOWN UNIVERSITY · PI PADMANABHAN, RADHAKRISHNAN · 2009 to 2010
$1.2M
Identification and Analysis of Flavivirus Protease and RNA Helicase InhibitorsR01AI070791 · NIAID · GEORGETOWN UNIVERSITY · PI PADMANABHAN, RADHAKRISHNAN · 2006 to 2009
$1.1M
Development of West Nile Virus/Broad Spectrum Flavivirus Protease InhibitorsR21AI109185 · NIAID · GEORGETOWN UNIVERSITY · PI PADMANABHAN, RADHAKRISHNAN · 2014 to 2015
$421k
NIAID NIH HHS R01 AI070791NIAID NIH HHS R21 AI109185NIAID NIH HHS U01 AI082068NIAID NIH HHS U54 AI057159
6 · The paper itself

Abstract

The mosquito-borne dengue virus serotypes 1-4 (DENV1-4) and West Nile virus (WNV) cause serious illnesses worldwide associated with considerable morbidity and mortality. According to the World Health Organization (WHO) estimates, there are about 390 million infections every year leading to ∼500,000 dengue haemorrhagic fever (DHF) cases and ∼25,000 deaths, mostly among children. Antiviral therapies could reduce the morbidity and mortality associated with flaviviral infections, but currently there are no drugs available for treatment. In this study, a high-throughput screening assay for the Dengue protease was employed to screen ∼120,000 small molecule compounds for identification of inhibitors. Eight of these inhibitors have been extensively analyzed for inhibition of the viral protease in vitro and cell-based viral replication using Renilla luciferase reporter replicon, infectivity (plaque) and cytotoxicity assays. Three of these compounds were identified as potent inhibitors of DENV and WNV proteases, and viral replication of DENV2 replicon and infectious RNA. Fluorescence quenching, kinetic analysis and molecular modeling of these inhibitors into the structure of NS2B-NS3 protease suggest a mode of inhibition for three compounds that they bind to the substrate binding pocket.

Indexed as

Antiviral AgentsBinding SitesDengue VirusDrug DiscoveryFlavivirusFluorescenceHigh-Throughput Screening AssaysKineticsLuciferases, RenillaModels, MolecularPeptide HydrolasesProtease InhibitorsRepliconSmall Molecule LibrariesViral Nonstructural ProteinsViral Plaque AssayAntiviral AgentsLuciferases, RenillaPeptide HydrolasesProtease InhibitorsSmall Molecule LibrariesViral Nonstructural ProteinsFluorescence quenchingHigh-throughput screeningProtease inhibitorsRenilla luciferase reporter repliconTherapeutic indexVirus infectivity assays

Identifiers

PMID27539384
PMCPMC5065773
OpenAlexW2514641087

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.