ArticlemSystems2019
Ifenprodil and Flavopiridol Identified by Genomewide RNA Interference Screening as Effective Drugs To Ameliorate Murine Acute Lung Injury after Influenza A H5N1 Virus Infection.
Article in mSystems, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Computational identification of novel therapeutic candidates for Streptococcus pyogenes and influenza A coinfections through transcriptomic-based drug repositioning.BMC microbiology · 2026Article
- Selective effects of cyclin dependent kinase inhibitors in gammaherpesvirus reactivation from latency.bioRxiv : the preprint server for biology · 2026Article
- Genome-Wide RNAi Screening Identifies Novel Host Factors Involved in Influenza A Virus Infection in A549 Cells.Viruses · 2026Article
- The self-assembled nanoparticle-based multi-epitope influenza mRNA vaccine elicits protective immunity against H1N1 and B influenza viruses in mice.Frontiers in immunology · 2024Article
- Production of Inhalable Ultra-Small Particles for Delivery of Anti-Inflammation Medicine via a Table-Top Microdevice.Micromachines · 2022Article
- R848 Adjuvant Laden With Self-Assembled Nanoparticle-Based mRNA Vaccine Elicits Protective Immunity Against H5N1 in Mice.Frontiers in immunology · 2022Article
- SARS-CoV-2: The Monster Causes COVID-19.Frontiers in cellular and infection microbiology · 2022Review
- Computational identification of repurposed drugs against viruses causing epidemics and pandemics via drug-target network analysis.Computers in biology and medicine · 2021Article
- Repurposed Drugs, Molecular Vaccines, Immune-Modulators, and Nanotherapeutics to Treat and Prevent COVID-19 Associated with SARS-CoV-2, a Deadly Nanovector.Advanced therapeutics · 2021Review
- Repurposing Sigma-1 Receptor Ligands for COVID-19 Therapy?Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to the limitations of effective treatments, avian influenza A H5N1 virus is the most lethal influenza virus strain that causes severe acute lung injury (ALI). To develop effective drugs ameliorating H5N1-induced ALI, we explore an RNA interference (RNAi) screening method to monitor changes in cell death induced by H5N1 infection. We performed RNAi screening on 19,424 genes in A549 lung epithelial cells and examined cell death induced by H5N1 infection. These screens identified 1,137 host genes for which knockdown altered cell viability by over 20%. DrugBank searches of these 1,137 host genes identified 146 validated druggable target genes with 372 drug candidates. We obtained 104 commercially available drugs with 65 validated target genes and examined their improvement of cell viability following H5N1 infection. We identified 28 drugs that could significantly recover cell viability following H5N1 infection and tested 10 in an H5N1-induced-ALI mouse model. The neurological drug ifenprodil and the anticancer drug flavopiridol markedly decreased leukocyte infiltration and lung injury scores in infected mouse lungs, significantly ameliorated edema in infected mouse lung tissues, and significantly improved the survival of H5N1-infected mice. Ifenprodil is an antagonist of the N-methyl-d-aspartate (NMDA) receptor, which is linked to inflammation and lung injury. Flavopiridol is an inhibitor of cyclin-dependent kinase 4 (CDK4), which is linked to leukocyte migration and lung injury. These results suggest that ifenprodil and flavopiridol represent novel remedies against potential H5N1 epidemics in addition to their proven indications. Furthermore, our strategy for identifying repurposable drugs could be a general approach for other diseases.
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Registered trials
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