ArticleJournal of virology2014
Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream mitogen-activated protein kinase signaling.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 51 citations in OpenAlex.
- Dengue Virus-Susceptible Animal Models: Research Progress, Core Bottlenecks, and Future Perspectives.Vaccines · 2026Review
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- Quantification of the interaction forces between dengue virus and dopamine type-2 receptor using optical tweezers.Virology journal · 2024Article
- Dengue virus: pathogenesis and potential for small molecule inhibitors.Bioscience reports · 2024Review
- The Raf kinase inhibitors Dabrafenib and Regorafenib impair Zika virus replication via distinct mechanisms.Journal of virology · 2024Article
- Machine learning and molecular docking prediction of potential inhibitors against dengue virus.Frontiers in chemistry · 2024Article
- Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview.Microorganisms · 2023Review
- Dopamine Receptor Ligand Selectivity-An In Silico/In Vitro Insight.Biomedicines · 2023Article
- COVID-19 and Parkinson's Disease: Possible Links in Pathology and Therapeutics.Neurotoxicity research · 2022Review
- Identification of Novel Dopamine DMolecules (Basel, Switzerland) · 2022Article
- Dengue Virus Replication Is Associated with Catecholamine Biosynthesis and Metabolism in Hepatocytes.Viruses · 2022Article
- Association of Hepatitis C Virus Replication with the Catecholamine Biosynthetic Pathway.Viruses · 2021Article
- Amaryllidaceae Alkaloid Cherylline Inhibits the Replication of Dengue and Zika Viruses.Antimicrobial agents and chemotherapy · 2021Article
- Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease.Viruses · 2021Article
- Review
- Heparanase, cell signaling, and viral infections.Cellular and molecular life sciences : CMLS · 2020Review
- Antiviral Activity of Compound L3 against Dengue and Zika Viruses In Vitro and In Vivo.International journal of molecular sciences · 2020Article
- Repurposing the Antiemetic Metoclopramide as an Antiviral Against Dengue Virus Infection in Neuronal Cells.Frontiers in cellular and infection microbiology · 2020Article
- Article
- Mast cell stabilizing effect of a geranyl acetophenone in dengue virus infection usingBioscience reports · 2019Article
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
Abstract
unlabelledDengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds-dihydrodibenzothiepines (DHBTs), identified through high-throughput screening-with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. IMPORTANCE: The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other compounds targeting the same cellular pathways, may have therapeutic potential for the treatment of dengue virus infections.
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.