ArticleScientific reports2019
Lack of selective resistance of influenza A virus in presence of host-targeted antiviral, UV-4B.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.Nature communications · 2020Pooled it
- 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
- Thapsigargin suppresses porcine hemagglutinating encephalomyelitis virus replication by disrupting host energy metabolism.Virologica Sinica · 2025Article
- Antiviral Compounds from Natural Sources Against Human Arboviruses: An Updated Review Including Illustrative In Silico Analysis.Pathogens (Basel, Switzerland) · 2025Review
- Strategies and efforts in circumventing the emergence of antiviral resistance against conventional antivirals.npj antimicrobials and resistance · 2025Review
- Genome-wide CRISPR/Cas9 screen identifies SLC39A9 and PIK3C3 as crucial entry factors for Ebola virus infection.PLoS pathogens · 2024Article
- Viral Evolution Shaped by Host Proteostasis Networks.Annual review of virology · 2023Review
- Article
- 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
- Transportin-3 Facilitates Uncoating of Influenza A Virus.International journal of molecular sciences · 2022Article
- Effect of SerialJournal of veterinary research · 2022Article
- Clinically Relevant Influenza Virus Evolution Reconstituted in a Human Lung Airway-on-a-Chip.Microbiology spectrum · 2021Article
- Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens.Bioorganic & medicinal chemistry · 2021Review
- Antiviral Evaluation of UV-4B and Interferon-Alpha Combination Regimens against Dengue Virus.Viruses · 2021Article
- Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses.Viruses · 2020Article
- Iminosugars: A host-targeted approach to combat Flaviviridae infections.Antiviral research · 2020Review
- Human Organs-on-Chips for Virology.Trends in microbiology · 2020Review
- Thapsigargin at Non-Cytotoxic Levels Induces a Potent Host Antiviral Response that Blocks Influenza A Virus Replication.Viruses · 2020Article
- The evolution of Tamiflu synthesis, 20 years on: Advent of enabling technologies the last piece of the puzzle?Tetrahedron · 2020Review
- Inhibition of Human Adenovirus Replication by the Importin α/β1 Nuclear Import Inhibitor Ivermectin.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Development of antiviral drug resistance is a continuous concern for viruses with high mutation rates such as influenza. The use of antiviral drugs targeting host proteins required for viral replication is less likely to result in the selection of resistant viruses than treating with direct-acting antivirals. The iminosugar UV-4B is a host-targeted glucomimetic that inhibits endoplasmic reticulum α-glucosidase I and II enzymes resulting in improper glycosylation and misfolding of viral glycoproteins. UV-4B has broad-spectrum antiviral activity against diverse viruses including dengue and influenza. To examine the ability of influenza virus to develop resistance against UV-4B, mouse-adapted influenza virus was passaged in mice in the presence or absence of UV-4B and virus isolated from lungs was used to infect the next cohort of mice, for five successive passages. Deep sequencing was performed to identify changes in the viral genome during passaging in the presence or absence of UV-4B. Relatively few minor variants were identified within each virus and the ratio of nonsynonymous to synonymous (dN/dS) substitutions of minor variants confirmed no apparent positive selection following sustained exposure to UV-4B. Three substitutions (one synonymous in PB2, one nonsynonymous in M and PA each) were specifically enriched (>3%) in UV-4B-treated groups at passage five. Recombinant viruses containing each individual or combinations of these nonsynonymous mutations remained sensitive to UV-4B treatment in mice. Overall, these data provide evidence that there is a high genetic barrier to the generation and selection of escape mutants following exposure to host-targeted iminosugar antivirals.
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