Evidence map›Paper›PMID 35177474›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Targeting ectromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia.

Pratikshya Pandey, Zahrah Al Rumaih, Ma Junaliah Tuazon Kels, Esther Ng, Rajendra Kc, Geeta Chaudhri, Gunasegaran Karupiah

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

14 citing papers in PubMed, 22 citations in OpenAlex.

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  14. Lucidenic acid A inhibits the binding of hACE2 receptor with spike protein to prevent SARS-CoV-2 invasion.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022
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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 at 2 institutions in 1 country.

Pratikshya PandeyViral Immunology and Immunopathology Group, Tasmanian School of Medicine, University of Tasmania, Hobart, TAS 7000, Australia.ORCID 0000-0003-4478-7581
Zahrah Al RumaihDepartment of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0002-6317-7749
Ma Junaliah Tuazon KelsDepartment of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0002-8730-1062
Esther NgDepartment of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0002-6607-3734
Rajendra KcViral Immunology and Immunopathology Group, Tasmanian School of Medicine, University of Tasmania, Hobart, TAS 7000, Australia.
Geeta ChaudhriDepartment of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0003-3388-2102
Gunasegaran KarupiahViral Immunology and Immunopathology Group, Tasmanian School of Medicine, University of Tasmania, Hobart, TAS 7000, Australia; Guna.Karupiah@utas.edu.au.ORCID 0000-0001-6306-4405
Australian National University · AUUniversity of Tasmania · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Viral causes of pneumonia pose constant threats to global public health, but there are no specific treatments currently available for the condition. Antivirals are ineffective when administered late after the onset of symptoms. Pneumonia is caused by an exaggerated inflammatory cytokine response to infection, but tissue necrosis and damage caused by virus also contribute to lung pathology. We hypothesized that viral pneumonia can be treated effectively if both virus and inflammation are simultaneously targeted. Combined treatment with the antiviral drug cidofovir and etanercept, which targets tumor necrosis factor (TNF), down-regulated nuclear factor kappa B-signaling and effectively reduced morbidity and mortality during respiratory ectromelia virus (ECTV) infection in mice even when treatment was initiated after onset of clinical signs. Treatment with cidofovir alone reduced viral load, but animals died from severe lung pathology. Treatment with etanercept had no effect on viral load but diminished levels of inflammatory cytokines and chemokines including TNF, IL-6, IL-1β, IL-12p40, TGF-β, and CCL5 and dampened activation of the STAT3 cytokine-signaling pathway, which transduces signals from multiple cytokines implicated in lung pathology. Consequently, combined treatment with a STAT3 inhibitor and cidofovir was effective in improving clinical disease and lung pathology in ECTV-infected mice. Thus, the simultaneous targeting of virus and a specific inflammatory cytokine or cytokine-signaling pathway is effective in the treatment of pneumonia. This approach might be applicable to pneumonia caused by emerging and re-emerging viruses, like seasonal and pandemic influenza A virus strains and severe acute respiratory syndrome coronavirus 2.

Indexed as

AnimalsAnti-Inflammatory Agents, Non-SteroidalAntiviral AgentsCell LineChlorocebus aethiopsCidofovirCytokinesDrug Evaluation, PreclinicalDrug Therapy, CombinationEctromelia virusEtanerceptFemaleLungMiceMice, Inbred C57BLNF-kappa BAnti-Inflammatory Agents, Non-SteroidalAntiviral AgentsCidofovirCytokinesEtanerceptNF-kappa BStat3 protein, mouseSTAT3 Transcription FactorTumor Necrosis Factor-alphacombined antiviral and anti-inflammatory drug treatmentdysregulated inflammatory cytokine responserespiratory ectromelia virus infectionTNF/NF-κB and STAT3 signaling pathwaysviral pneumonia

Identifiers

PMID35177474
PMCPMC8872766
OpenAlexW4213029312

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.