Evidence map›Paper›PMID 29665374›Full record

ArticleAntiviral research2018

Spectrum of activity testing for therapeutics against all four dengue virus serotypes in AG129 mouse models: Proof-of-concept studies with the adenosine nucleoside inhibitor NITD-008.

Gregg N Milligan, Mellodee White, Diana Zavala, Richard B Pyles, Vanessa V Sarathy, Alan D T Barrett, Nigel Bourne

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antiviral research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

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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

7 authors.

Gregg N MilliganDepartment of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Mellodee WhiteDepartment of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Diana ZavalaDepartment of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA.
Richard B PylesDepartment of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Vanessa V SarathySealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Alan D T BarrettSealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Nigel BourneDepartment of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: nibourne@utmb.edu.

Funding

Training in Emerging Infectious Diseases and BiodefenseT32AI007536 · NIAID · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI WHITE, ARTHUR CLINTON · 1998 to 2013
$4.1M
NIAID NIH HHS HHSN272201000040I-27200009NIAID NIH HHS N01 AI030065NIAID NIH HHS T32 AI007536
6 · The paper itself

Abstract

Dengue is a mosquito-borne disease of global public health importance caused by four genetically and serologically related viruses (DENV-1 to DENV-4). Efforts to develop effective vaccines and therapeutics for dengue have been slowed by the paucity of preclinical models that mimic human disease. DENV-2 models in interferon receptor deficient AG129 mice were an important advance but only allowed testing against a single DENV serotype. We have developed complementary AG129 mouse models of severe disseminated dengue infection using strains of the other three DENV serotypes. Here we used the adenosine nucleoside inhibitor NITD-008 to show that these models provide the ability to perform comparative preclinical efficacy testing of candidate antivirals in vivo against the full-spectrum of DENV serotypes. Although NITD-008 was effective in modulating disease caused by all DENV serotypes, the variability in protection among DENV serotypes was greater than expected from differences in activity in in vitro testing studies emphasizing the need to undertake spectrum of activity testing to help in prioritization of candidate compounds for further development.

Indexed as

Disease Models, AnimalAdenosineAnimalsAntiviral AgentsDengue VirusDrug Evaluation, PreclinicalMiceNucleic Acid Synthesis InhibitorsProof of Concept StudySerogroupSevere DengueAdenosineAntiviral AgentsNucleic Acid Synthesis InhibitorsAnimal modelAntiviral testingDengue virusFlavivirusPreclinical development

Identifiers

PMID29665374
PMCPMC6685202

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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.