Evidence map›Paper›PMID 29579332›Full record

ArticleBritish journal of pharmacology2018

Late therapeutic intervention with a respiratory syncytial virus L-protein polymerase inhibitor, PC786, on respiratory syncytial virus infection in human airway epithelium.

Daniel W Brookes, Matthew Coates, Heather Allen, Leah Daly, Samuel Constant, Song Huang, Mark Hows, Amanda Davis, Lindsey Cass, John Ayrton and 4 more

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

Article in British journal of pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

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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

14 authors at 3 institutions in 3 countries.

Daniel W BrookesPulmocide Limited, London, UK.
Matthew CoatesPulmocide Limited, London, UK.
Heather AllenPulmocide Limited, London, UK.
Leah DalyPulmocide Limited, London, UK.
Samuel ConstantEpithelix Sarl, Geneva, Switzerland.
Song HuangEpithelix Sarl, Geneva, Switzerland.
Mark HowsLGC Limited, Fordham, UK.
Amanda DavisPulmocide Limited, London, UK.
Lindsey CassPulmocide Limited, London, UK.
John AyrtonPulmocide Limited, London, UK.
Ian KnowlesPneumolabs Limited, Harrow, UK.
Pete StrongPulmocide Limited, London, UK.
Garth RapeportPulmocide Limited, London, UK.
Kazuhiro ItoPulmocide Limited, London, UK.ORCID 0000-0001-9320-2717
Shanghai Pesticide Research Institute · CNMédecins Sans Frontières · CHArrow International (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeEffective anti-respiratory syncytial virus (RSV) agents are still not available for clinical use. Current major targets are virus surface proteins, such as a fusion protein involved in viral entry, but agents effective after RSV infection is established are required. Here we have investigated the effects of late therapeutic intervention with a novel inhaled RSV polymerase inhibitor, PC786, on RSV infection in human airway epithelium. EXPERIMENTAL APPROACH: Air liquid interface-cultured bronchial or small airway epithelium was infected with RSVA2. PC786 was applied apically or basolaterally once daily following peak virus load on Day 3 post inoculation. Apical wash was collected daily for determination of viral burden by PCR and plaque assay (primary endpoints) and biomarker analyses. The effects were compared with those of ALS-8112, an anti-RSV nucleoside analogue, and GS-5806, a fusion-protein inhibitor, which were treated basolaterally. KEY

resultsLate intervention with GS-5806 did not show significant anti-viral effects, but PC786 produced potent, concentration-dependent inhibition of viral replication with viral load falling below detectable limits 3 days after treatment commenced in airway epithelium. These effects were superior to those of ALS-8112. PC786 showed inhibitory activities against RSV-induced increases of CCL5, IL-6, double-strand DNA and mucin. The effects of PC786 were also confirmed in small airway epithelium. CONCLUSION AND IMPLICATIONS: Late therapeutic intervention with the RSV polymerase inhibitor, PC786, reduced the viral burden quickly in human airway epithelium. Thus, PC786 demonstrates the potential to be an effective therapeutic agent to treat active RSV infection.

Indexed as

Antiviral AgentsBenzamidesBenzazepinesDNA-Directed RNA PolymerasesDose-Response Relationship, DrugEpitheliumHeLa CellsHumansMicrobial Sensitivity TestsRespiratory MucosaRespiratory Syncytial Virus, HumanRespiratory Syncytial Virus InfectionsSpiro CompoundsStructure-Activity RelationshipVirus ReplicationAntiviral AgentsBenzamidesBenzazepinesDNA-Directed RNA PolymerasesPC-786Spiro Compounds

Identifiers

PMID29579332
PMCPMC5980447
OpenAlexW2789240485

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.