ArticlePLoS pathogens2019
RNAi-based small molecule repositioning reveals clinically approved urea-based kinase inhibitors as broadly active antivirals.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 34 citations in OpenAlex.
- Puumala orthohantavirus: prevalence, biology, disease, animal models and recent advances in therapeutics development and structural biology.Frontiers in immunology · 2025Review
- Identification of diphenylurea derivatives as novel endocytosis inhibitors that demonstrate broad-spectrum activity against SARS-CoV-2 and influenza A virus both in vitro and in vivo.PLoS pathogens · 2023Article
- Upregulation of galectin-3 in influenza A virus infection promotes viral RNA synthesis through its association with viral PA protein.Journal of biomedical science · 2023Article
- Influenza A virus replication has a stronger dependency on Raf/MEK/ERK signaling pathway activity than SARS-CoV-2.Frontiers in cellular and infection microbiology · 2023Article
- Cellular glycan modification by B3GAT1 broadly restricts influenza virus infection.Nature communications · 2022Article
- Article
- A genome-wide CRISPR/Cas9 gene knockout screen identifies immunoglobulin superfamily DCC subclass member 4 as a key host factor that promotes influenza virus endocytosis.PLoS pathogens · 2021Article
- Restriction factor compendium for influenza A virus reveals a mechanism for evasion of autophagy.Nature microbiology · 2021Article
- Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach.Scientific reports · 2021Article
- A painful lesson from the COVID-19 pandemic: the need for broad-spectrum, host-directed antivirals.Journal of translational medicine · 2020Article
- Identification of new drug treatments to combat COVID19: A signature-based approach using iLINCS.Research square · 2020Article
- Identification of amitriptyline HCl, flavin adenine dinucleotide, azacitidine and calcitriol as repurposing drugs for influenza A H5N1 virus-induced lung injury.PLoS pathogens · 2020Article
- Drug targets for COVID-19 therapeutics: Ongoing global efforts.Journal of biosciences · 2020Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Influenza viruses (IVs) tend to rapidly develop resistance to virus-directed vaccines and common antivirals targeting pathogen determinants, but novel host-directed approaches might preclude resistance development. To identify the most promising cellular targets for a host-directed approach against influenza, we performed a comparative small interfering RNA (siRNA) loss-of-function screen of IV replication in A549 cells. Analysis of four different IV strains including a highly pathogenic avian H5N1 strain, an influenza B virus (IBV) and two human influenza A viruses (IAVs) revealed 133 genes required by all four IV strains. According to gene enrichment analyses, these strain-independent host genes were particularly enriched for nucleocytoplasmic trafficking. In addition, 360 strain-specific genes were identified with distinct patterns of usage for IAVs versus IBV and human versus avian IVs. The strain-independent host genes served to define 43 experimental and otherwise clinically approved drugs, targeting reportedly fourteen of the encoded host factors. Amongst the approved drugs, the urea-based kinase inhibitors (UBKIs) regorafenib and sorafenib exhibited a superior therapeutic window of high IV antiviral activity and low cytotoxicity. Both UBKIs appeared to block a cell signaling pathway involved in IV replication after internalization, yet prior to vRNP uncoating. Interestingly, both compounds were active also against unrelated viruses including cowpox virus (CPXV), hantavirus (HTV), herpes simplex virus 1 (HSV1) and vesicular stomatitis virus (VSV) and showed antiviral efficacy in human primary respiratory cells. An in vitro resistance development analysis for regorafenib failed to detect IV resistance development against this drug. Taken together, the otherwise clinically approved UBKIs regorafenib and sorafenib possess high and broad-spectrum antiviral activity along with substantial robustness against resistance development and thus constitute attractive host-directed drug candidates against a range of viral infections including influenza.
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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 Socratic graph.