Evidence map›Paper›PMID 42215780›Full record

Articlenpj antimicrobials and resistance2026

Polymerase-inhibitor drug synergy and mutational signatures in different epithelial cell models of RSVA and hPIV3 infection.

Samuel Ellis, Amy I Jacobs, Shengyuan Zhang, Laura Buggiotti, Maximillian Woodall, Jila Ajeian, Helena Tutill, Charles Miller, Machaela Palor, Angelika Kopec and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in npj antimicrobials and resistance, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

19 authors.

Samuel Ellis *Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK. samuel.ellis@ucl.ac.uk.
Amy I Jacobs *Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Shengyuan ZhangDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Laura BuggiottiDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Maximillian WoodallDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Jila AjeianDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Helena TutillDepartment of Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK.
Charles MillerGreat Ormond Street Hospital NHS Foundation Trust, London, UK.
Machaela PalorDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Angelika KopecGreat Ormond Street Hospital NHS Foundation Trust, London, UK.
Elizabeth K HaugheyDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Hongxia MaDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Arushi SharmaDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Mia TomlinsonDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Rachel WilliamsDepartment of Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK.
Christopher O'CallaghanDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Joseph F StandingDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK.
Claire M SmithDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK. c.m.smith@ucl.ac.uk.
Judith BreuerDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, UK. j.breuer@ucl.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the huge global health burden presented by respiratory viruses, effective broad-spectrum antiviral therapeutic options remain limited. Here we evaluated the antiviral activity of four RNA-dependent RNA polymerase (RdRp) inhibitors, remdesivir, ribavirin, favipiravir, and molnupiravir, as monotherapy or dual-drug combinations against respiratory syncytial virus (subtype A, RSVA) and human parainfluenza (serotype 3, hPIV3) using epithelial cell lines and primary human airway culture models. Remdesivir showed the greatest potency across both viruses, while ribavirin and favipiravir also demonstrated inhibition. Molnupiravir was active against RSVA but not hPIV3. Several dual-drug combinations, including remdesivir-favipiravir, remdesivir-molnupiravir and favipiravir-molnupiravir, produced marked synergy against RSVA, and more limited synergy for hPIV3. Antiviral efficacy was validated in primary airway epithelial cultures, where effective concentrations preserved epithelial integrity and attenuated viral disruption of ciliary function. Across both viruses, increasing antiviral exposure was associated with dose-dependent signature mutagenesis. Antivirals induced significantly higher RSVA mutation burden in the primary airway model. These findings highlight the therapeutic potential of RdRp inhibitor combinations for RSVA and hPIV3, provide mechanistic insight through antiviral-related mutational signatures, and demonstrate advantages of the primary human airway culture model for development of effective multi-drug regimens and broad-spectrum antiviral preparedness.

Identifiers

PMID42215780
PMCPMC13530243

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.