ArticleCells2019
Novel Flavivirus Antiviral That Targets the Host Nuclear Transport Importin α/β1 Heterodimer.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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.
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.
Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Membrane Perturbations and Assay Interferences by Ivermectin Explain Its In Vitro SARS-CoV-2 Antiviral Activities and Lack of Translatability.Journal of medicinal chemistry · 2025Review
- Cytoplasmic retention of dengue virus capsid protein by metformin impairing nuclear transport.The Journal of general virology · 2025Article
- Advances in antiviral strategies targeting mosquito-borne viruses: cellular, viral, and immune-related approaches.Virology journal · 2025Review
- Review
- Article
- PCV2 Cap protein nuclear import via importin α/β receptor: molecular insights and antiviral potential.Frontiers in microbiology · 2025Article
- Animal Models, Therapeutics, and Vaccine Approaches to Emerging and Re-Emerging Flaviviruses.Viruses · 2024Review
- Succinylation modification: a potential therapeutic target in stroke.Neural regeneration research · 2024Review
- Increased In Vivo Exposure of N-(4-Hydroxyphenyl) Retinamide (4-HPR) to Achieve Plasma Concentrations Effective against Dengue Virus.Pharmaceutics · 2023Article
- An Elusive Target: Inhibitors of JC Polyomavirus Infection and Their Development as Therapeutics for the Treatment of Progressive Multifocal Leukoencephalopathy.International journal of molecular sciences · 2023Review
- Article
- Differential Gene Expression Pattern of Importin β3 and NS5 in C6/36 Cells Acutely and Persistently Infected with Dengue Virus 2.Pathogens (Basel, Switzerland) · 2023Article
- Conservation of Importin α Function in Apicomplexans: Ivermectin and GW5074 TargetInternational journal of molecular sciences · 2022Article
- Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets.Journal of biomolecular structure & dynamics · 2022Article
- Potential therapeutic effects of Ivermectin in COVID-19.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Review
- Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Article
- Article
- Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication.Biochimica et biophysica acta. Molecular basis of disease · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue virus (DENV) threatens almost 70% of the world's population, with no effective vaccine or therapeutic currently available. A key contributor to infection is nuclear localisation in the infected cell of DENV nonstructural protein 5 (NS5) through the action of the host importin (IMP) α/β1 proteins. Here, we used a range of microscopic, virological and biochemical/biophysical approaches to show for the first time that the small molecule GW5074 has anti-DENV action through its novel ability to inhibit NS5⁻IMPα/β1 interaction in vitro as well as NS5 nuclear localisation in infected cells. Strikingly, GW5074 not only inhibits IMPα binding to IMPβ1, but can dissociate preformed IMPα/β1 heterodimer, through targeting the IMPα armadillo (ARM) repeat domain to impact IMPα thermal stability and α-helicity, as shown using analytical ultracentrifugation, thermostability analysis and circular dichroism measurements. Importantly, GW5074 has strong antiviral activity at low µM concentrations against not only DENV-2, but also zika virus and West Nile virus. This work highlights DENV NS5 nuclear targeting as a viable target for anti-flaviviral therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
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.