Evidence map›Paper›PMID 24065587›Full record

ArticlePharmaceutical research2014

Zanamivir conjugated to poly-L-glutamine is much more active against influenza viruses in mice and ferrets than the drug itself.

Alisha K Weight, Jessica A Belser, Terrence M Tumpey, Jianzhu Chen, Alexander M Klibanov

Abstract read
In one paragraph

Article in Pharmaceutical research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.4field-weighted citation impact, top 33% 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

2 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Polyglutamine Repeats in Viruses.Molecular neurobiology · 2019
    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 3 institutions in 1 country.

Alisha K WeightDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA.
Jessica A Belser
Terrence M Tumpey
Jianzhu Chen
Alexander M Klibanov
Massachusetts Institute of Technology · USCenters for Disease Control and Prevention · USNational Center for Immunization and Respiratory Diseases · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Bi-functional Polymer-Attached Inhibitors of Influenza VirusesU01AI074443 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI CHEN, JIANZHU · 2007 to 2011
$3.7M
NCI NIH HHS P30 CA014051NIAID NIH HHS U01 AI074443NIAID NIH HHS U01-AI074443
6 · The paper itself

Abstract

purposePreviously, polymer-attached zanamivir had been found to inhibit influenza A viruses in vitro far better than did small-molecule zanamivir (1) itself. The aim of this study was to identify in vitro-using the plaque reduction assay-a highly potent 1-polymer conjugate, and subsequently test its antiviral efficacy in vivo.

methodsBy examining the structure-activity relationship of 1-polymer conjugates in the plaque assay, we have determined that the most potent inhibitor against several representative influenza virus strains has a neutral high-molecular-weight backbone and a short alkyl linker. We have examined this optimal polymeric inhibitor for efficacy and immunogenicity in the mouse and ferret models of infection.

results1 attached to poly-L-glutamine is an effective therapeutic for established influenza infection in ferrets, reducing viral titers up to 30-fold for 6 days. There is also up to a 190-fold reduction in viral load when the drug is used as a combined prophylactic/therapeutic in mice. Additionally, we see no evidence that the drug conjugate stimulates an immune response in mice upon repeat administration.

conclusions1 attached to a neutral high-molecular-weight backbone through a short alkyl linker drastically reduced both in vitro and in vivo titers compared to those observed with 1 itself. Thus, further development of this polymeric zanamivir for the mitigation of influenza infection seems warranted.

Indexed as

AnimalsAntiviral AgentsFerretsGlutamineInfluenza A virusMaleMiceMice, Inbred BALB COrthomyxoviridae InfectionsStructure-Activity RelationshipZanamivirAntiviral AgentsGlutamineZanamivir

Identifiers

PMID24065587
PMCPMC3964776
OpenAlexW2040431650

What OpenQuestion holds

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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.