Evidence map›Paper›PMID 25451059›Full record

ArticleAntimicrobial agents and chemotherapy2015

Synergistic effect of nitazoxanide with neuraminidase inhibitors against influenza A viruses in vitro.

Giuseppe Belardo, Orlando Cenciarelli, Simone La Frazia, Jean Francois Rossignol, M Gabriella Santoro

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

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 6% 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

51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Progress of Influenza Viruses and Inhibitors.Current medicinal chemistry · 2025
    Review
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  12. Antiviral activity of nitazoxanide againstJournal of virus eradication · 2023
    Article
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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

5 authors at 3 institutions in 2 countries.

Giuseppe BelardoDepartment of Biology, University of Rome Tor Vergata, Rome, Italy.
Orlando CenciarelliDepartment of Biology, University of Rome Tor Vergata, Rome, Italy.
Simone La FraziaDepartment of Biology, University of Rome Tor Vergata, Rome, Italy.
Jean Francois RossignolRomark Laboratories, LC, Tampa, Florida, USA.
M Gabriella SantoroDepartment of Biology, University of Rome Tor Vergata, Rome, Italy Institute of Translational Pharmacology, CNR, Rome, Italy santoro@bio.uniroma2.it.
University of Rome Tor Vergata · ITIstituto di Farmacologia Traslazionale · ITRomark (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The emergence of drug-resistant influenza A virus (IAV) strains represents a serious threat to global human health and underscores the need for novel approaches to anti-influenza chemotherapy. Combination therapy with drugs affecting different IAV targets represents an attractive option for influenza treatment. We have previously shown that the thiazolide anti-infective nitazoxanide (NTZ) inhibits H1N1 IAV replication by selectively blocking viral hemagglutinin maturation. Herein we investigate the anti-influenza activity of NTZ against a wide range of human and avian IAVs (H1N1, H3N2, H5N9, H7N1), including amantadine-resistant and oseltamivir-resistant strains, in vitro. We also investigate whether therapy with NTZ in combination with the neuraminidase inhibitors oseltamivir and zanamivir exerts synergistic, additive, or antagonistic antiviral effects against influenza viruses. NTZ was effective against all IAVs tested, with 50% inhibitory concentrations (IC50s) ranging from 0.9 to 3.2 μM, and selectivity indexes (SIs) ranging from >50 to >160, depending on the strain and the multiplicity of infection (MOI). Combination therapy studies were performed in cell culture-based assays using A/Puerto Rico/8/1934 (H1N1), A/WSN/1933 (H1N1), or avian A/chicken/Italy/9097/1997 (H5N9) IAVs; dose-effect analysis and synergism/antagonism quantification were performed using isobologram analysis according to the Chou-Talalay method. Combination index (CI) analysis indicated that NTZ and oseltamivir combination treatment was synergistic against A/Puerto Rico/8/1934 (H1N1) and A/WSN/1933 (H1N1) IAVs, with CI values ranging between 0.39 and 0.63, independently of the MOI used. Similar results were obtained when NTZ was administered in combination with zanamivir (CI=0.3 to 0.48). NTZ-oseltamivir combination treatment was synergistic also against the avian A/chicken/Italy/9097/1997 (H5N9) IAV (CI=0.18 to 0.31). Taken together, the results suggest that regimens that combine neuraminidase inhibitors and nitazoxanide exert synergistic anti-influenza effects.

Indexed as

Antiviral AgentsHumansInfluenza A virusInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H3N2 SubtypeInfluenza A Virus, H7N1 SubtypeNeuraminidaseNitro CompoundsOseltamivirThiazolesZanamivirAntiviral AgentsNeuraminidasenitazoxanideNitro CompoundsOseltamivirThiazolesZanamivir

Identifiers

PMID25451059
PMCPMC4335909
OpenAlexW1989043263

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.