ArticlePLoS neglected tropical diseases2016
Iminosugars Inhibit Dengue Virus Production via Inhibition of ER Alpha-Glucosidases--Not Glycolipid Processing Enzymes.
Article in PLoS neglected tropical diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 84 citations in OpenAlex.
- Randomized single oral dose phase 1 study of safety, tolerability, and pharmacokinetics of Iminosugar UV-4 Hydrochloride (UV-4B) in healthy subjects.PLoS neglected tropical diseases · 2022Trial
- Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients.PLoS neglected tropical diseases · 2016Trial
- Maltase 1 regulates DENV2 infection and life history in Aedes aegypti.Insect science · 2026Article
- Off-Target Binding of Miglustat to Glycogen Debranching Enzyme.International journal of molecular sciences · 2026Article
- Review
- Exploring Small-Molecule Inhibitors of Glucosidase II: Advances, Challenges, and Therapeutic Potential in Cancer and Viral Infection.International journal of molecular sciences · 2025Review
- Antiviral Compounds from Natural Sources Against Human Arboviruses: An Updated Review Including Illustrative In Silico Analysis.Pathogens (Basel, Switzerland) · 2025Review
- The Sweet Aspects of Orthoflavivirus Treatment Design and Vaccine Development.Journal of medical virology · 2025Review
- Rational design, synthesis, in vitro, and in-silico studies of pyrazole‑phthalazine hybrids as new α‑glucosidase inhibitors.Scientific reports · 2025Article
- Identification of Three Novel O-Linked Glycans in the Envelope Protein of Tick-Borne Encephalitis Virus.Viruses · 2024Article
- Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Expanding horizons of iminosugars as broad-spectrum anti-virals: mechanism, efficacy and novel developments.Natural products and bioprospecting · 2024Review
- Deciphering Molecular Aspects of PotentialMetabolites · 2023Article
- Review
- Exploring the Potential of Iminosugars as Antivirals for Crimean-Congo Haemorrhagic Fever Virus, Using the Surrogate Hazara Virus: Liquid-Chromatography-Based Mapping of Viral N-Glycosylation and In Vitro Antiviral Assays.Pathogens (Basel, Switzerland) · 2023Article
- Antiviral activity of glucosylceramide synthase inhibitors in alphavirus infection of the central nervous system.Brain communications · 2023Article
- Antiviral plant-derived natural products to combat RNA viruses: Targets throughout the viral life cycle.Letters in applied microbiology · 2022Review
- The primary familial brain calcification-associated protein MYORG is an α-galactosidase with restricted substrate specificity.PLoS biology · 2022Article
- Antiviral effects of deoxynojirimycin (DNJ)-based iminosugars in dengue virus-infected primary dendritic cells.Antiviral research · 2022Article
- Crystal polymorphism in fragment-based lead discovery of ligands of the catalytic domain of UGGT, the glycoprotein folding quality control checkpoint.Frontiers in molecular biosciences · 2022Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
It has long been thought that iminosugar antiviral activity is a function of inhibition of endoplasmic reticulum-resident α-glucosidases, and on this basis, many iminosugars have been investigated as therapeutic agents for treatment of infection by a diverse spectrum of viruses, including dengue virus (DENV). However, iminosugars are glycomimetics possessing a nitrogen atom in place of the endocyclic oxygen atom, and the ubiquity of glycans in host metabolism suggests that multiple pathways can be targeted via iminosugar treatment. Successful treatment of patients with glycolipid processing defects using iminosugars highlights the clinical exploitation of iminosugar inhibition of enzymes other than ER α-glucosidases. Evidence correlating antiviral activity with successful inhibition of ER glucosidases together with the exclusion of alternative mechanisms of action of iminosugars in the context of DENV infection is limited. Celgosivir, a bicyclic iminosugar evaluated in phase Ib clinical trials as a therapeutic for the treatment of DENV infection, was confirmed to be antiviral in a lethal mouse model of antibody-enhanced DENV infection. In this study we provide the first evidence of the antiviral activity of celgosivir in primary human macrophages in vitro, in which it inhibits DENV secretion with an EC50 of 5 μM. We further demonstrate that monocyclic glucose-mimicking iminosugars inhibit isolated glycoprotein and glycolipid processing enzymes and that this inhibition also occurs in primary cells treated with these drugs. By comparison to bicyclic glucose-mimicking iminosugars which inhibit glycoprotein processing but do not inhibit glycolipid processing and galactose-mimicking iminosugars which do not inhibit glycoprotein processing but do inhibit glycolipid processing, we demonstrate that inhibition of endoplasmic reticulum-resident α-glucosidases, not glycolipid processing, is responsible for iminosugar antiviral activity against DENV. Our data suggest that inhibition of ER α-glucosidases prevents release of virus and is the primary antiviral mechanism of action of iminosugars against DENV.
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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.