ArticlePLoS pathogens2020
Identification of amitriptyline HCl, flavin adenine dinucleotide, azacitidine and calcitriol as repurposing drugs for influenza A H5N1 virus-induced lung injury.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 101 citations in OpenAlex.
- Pooled it
- The role of vitamin D deficiency on COVID-19: a systematic review and meta-analysis of observational studies.Epidemiology and health · 2021Pooled it
- Could antidepressants increase mood and immunity at the same time?Frontiers in psychiatry · 2025Review
- Gene expression profile analysis of severe influenza-based modulation of idiopathic pulmonary fibrosis.European journal of medical research · 2024Article
- A brief overview of SARS-CoV-2 infection and its management strategies: a recent update.Molecular and cellular biochemistry · 2024Review
- Pathogenesis of COVID19 and the applications of US FDA-approved repurposed antiviral drugs to combat SARS-CoV-2 in Saudi Arabia: A recent update by review of literature.Saudi journal of biological sciences · 2024Review
- Unveiling the Role of Exosomes in the Pathophysiology of Sepsis: Insights into Organ Dysfunction and Potential Biomarkers.International journal of molecular sciences · 2024Review
- Calcitriol ameliorates motor deficits and prolongs survival of Chrne-deficient mouse, a model for congenital myasthenic syndrome, by inducing Rspo2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Nano-based techniques: A revolutionary approach to prevent covid-19 and enhancing human awareness.Journal of drug delivery science and technology · 2023Review
- High-dose vitamin D supplementation is related to an improvement in serum alkaline phosphatase in COVID-19 patients; a randomized double-blinded clinical trial.Journal of health, population, and nutrition · 2023Article
- Antibiotic Utilization during COVID-19: Are We Over-Prescribing?Antibiotics (Basel, Switzerland) · 2023Article
- Global Effect of COVID-19 Pandemic on Cancer Patients and its Treatment: A Systematic Review.Clinical complementary medicine and pharmacology · 2022Review
- Recent review of COVID-19 management: diagnosis, treatment and vaccination.Pharmacological reports : PR · 2022Review
- DeepLPI: a novel deep learning-based model for protein-ligand interaction prediction for drug repurposing.Scientific reports · 2022Article
- Identification of Diosmin and Flavin Adenine Dinucleotide as Repurposing Treatments for Monkeypox Virus: A Computational Study.International journal of molecular sciences · 2022Article
- Combined deep learning and molecular docking simulations approach identifies potentially effective FDA approved drugs for repurposing against SARS-CoV-2.Computers in biology and medicine · 2022Article
- Golden opportunity for intervention? Identifying vitamin D deficiency in patients with substance use disorders in hospital.BMJ open quality · 2022Article
- Repurposing Thalidomide, its Analogue and Apremilast for Possible Antiviral in Situation of Severe COVID Cytokine Syndrome.Infectious disorders drug targets · 2022Article
- Riboflavin for COVID-19 Adjuvant Treatment in Patients With Mental Health Disorders: Observational Study.Frontiers in pharmacology · 2022Article
- Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques.Journal of inflammation research · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infection with avian influenza A H5N1 virus results in acute lung injury (ALI) and has a high mortality rate (52.79%) because there are limited therapies available for treatment. Drug repositioning is an economical approach to drug discovery. We developed a method for drug repositioning based on high-throughput RNA sequencing and identified several drugs as potential treatments for avian influenza A H5N1 virus. Using high-throughput RNA sequencing, we identified a total of 1,233 genes differentially expressed in A549 cells upon H5N1 virus infection. Among these candidate genes, 79 drug targets (corresponding to 59 approved drugs) overlapped with the DrugBank target database. Twenty-two of the 41 commercially available small-molecule drugs reduced H5N1-mediated cell death in cultured A549 cells, and fifteen drugs that protected A549 cells when administered both pre- and post-infection were tested in an H5N1-infection mouse model. The results showed significant alleviation of acute lung injury by amitriptyline HCl (an antidepressant drug), flavin adenine dinucleotide (FAD; an ophthalmic agent for vitamin B2 deficiency), azacitidine (an anti-neoplastic drug) and calcitriol (an active form of vitamin D). All four agents significantly reduced the infiltrating cell count and decreased the lung injury score in H5N1 virus-infected mice based on lung histopathology, significantly improved mouse lung edema by reducing the wet-to-dry weight ratio of lung tissue and significantly improved the survival of H5N1 virus-infected mice. This study not only identifies novel potential therapies for influenza H5N1 virus-induced lung injury but also provides a highly effective and economical screening method for repurposing drugs that may be generalizable for the prevention and therapy of other diseases.
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Registered trials
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.