ArticleVirology journal2015
A small molecule inhibitor of dengue virus type 2 protease inhibits the replication of all four dengue virus serotypes in cell culture.
Article in Virology journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 61 citations in OpenAlex.
- Achievements and Approaches in the Search for Small-Molecule Dengue NS2B/NS3 Inhibitors.Current medicinal chemistry · 2026Review
- A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.Viruses · 2025Review
- Dengue virus: pathogenesis and potential for small molecule inhibitors.Bioscience reports · 2024Review
- Synthesis and biological activity of imidazole phenazine derivatives as potential inhibitors for NS2B-NS3 dengue protease.Heliyon · 2024Article
- Ascorbic acid as serine protease inhibitor in lung cancer cell line and human serum albumin.PloS one · 2024Article
- Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview.Microorganisms · 2023Review
- Review
- Assessing the potential of NS2B/NS3 protease inhibitors biomarker in curbing dengue virus infections:Frontiers in cellular and infection microbiology · 2023Review
- Structure of the dengue virus RNA promoter.RNA (New York, N.Y.) · 2022Article
- Phytochemical Compound Screening to Identify Novel Small Molecules against Dengue Virus: A Docking and Dynamics Study.Molecules (Basel, Switzerland) · 2022Article
- Evaluation of Melongosides as Potential Inhibitors of NS2B-NS3 Activator-Protease of Dengue Virus (Serotype 2) by Using Molecular Docking and Dynamics Simulation Approach.Journal of tropical medicine · 2022Article
- Updates on Dengue Vaccine and Antiviral: Where Are We Heading?Molecules (Basel, Switzerland) · 2021Review
- A short survey of dengue protease inhibitor development in the past 6 years (2015-2020) with an emphasis on similarities between DENV and SARS-CoV-2 proteases.Bioorganic & medicinal chemistry · 2021Review
- Viral proteases: Structure, mechanism and inhibition.The Enzymes · 2021Article
- Computational screening of medicinal plant phytochemicals to discover potent pan-serotype inhibitors against dengue virus.Scientific reports · 2019Article
- Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling.PloS one · 2019Article
- Roles and Prospects of Dengue Virus Non-structural Proteins as Antiviral Targets: An Easy Digest.The Malaysian journal of medical sciences : MJMS · 2018Review
- Small-Molecule Dengue Virus Co-imprinting and Its Application as an Electrochemical Sensor.ChemistryOpen · 2017Article
- Open drug discovery for the Zika virus.F1000Research · 2016Article
- A critical review on serine protease: Key immune manipulator and pathology mediator.Allergologia et immunopathologiaReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDengue has emerged as the most significant of arboviral diseases in the 21st century. It is endemic to >100 tropical and sub-tropical countries around the world placing an estimated 3.6 billion people at risk. It is caused by four genetically similar but antigenically distinct, serotypes of dengue viruses. There is neither a vaccine to prevent nor a drug to treat dengue infections, at the present time. The major objective of this work was to explore the possibility of identifying a small molecule inhibitor of the dengue virus protease and assessing its ability to suppress viral replication in cultured cells.
methodsWe cloned, expressed and purified recombinant dengue virus type 2 protease. Using an optimized and validated fluorogenic peptide substrate cleavage assay to monitor the activity of this cloned dengue protease we randomly screened ~1000 small molecules from an 'in-house' library to identify potential dengue protease inhibitors.
resultsA benzimidazole derivative, named MB21, was found to be the most potent in inhibiting the cloned protease (IC₅₀ = 5.95 μM). In silico docking analysis indicated that MB21 binds to the protease in the vicinity of the active site. Analysis of kinetic parameters of the enzyme reaction suggested that MB21 presumably functions as a mixed type inhibitor. Significantly, this molecule identified as an inhibitor of dengue type 2 protease was also effective in inhibiting each one of the four serotypes of dengue viruses in infected cells in culture, based on analysis of viral antigen synthesis and infectious virus production. Interestingly, MB21 did not manifest any discernible cytotoxicity.
conclusionsThis work strengthens the notion that a single drug molecule can be effective against all four dengue virus serotypes. The molecule MB21 could be a potential candidate for 'hit-to-lead' optimization, and may pave the way towards developing a pan-dengue virus antiviral drug.
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.