ArticlePLoS neglected tropical diseases2018
Nucleobases and corresponding nucleosides display potent antiviral activities against dengue virus possibly through viral lethal mutagenesis.
Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- Purine but Not Pyrimidine De Novo Nucleotide Biosynthesis Inhibitors Strongly Enhance the Antiviral Effect of Corresponding Nucleobases Against Dengue Virus.Molecules (Basel, Switzerland) · 2025Article
- Dengue virus: pathogenesis and potential for small molecule inhibitors.Bioscience reports · 2024Review
- Insights into targeting SARS-CoV-2: design, synthesis,RSC medicinal chemistry · 2023Article
- Review
- Lethal Mutagenesis of RNA Viruses and Approved Drugs with Antiviral Mutagenic Activity.Viruses · 2022Review
- Enhancing the Antiviral Potency of Nucleobases for Potential Broad-Spectrum Antiviral Therapies.Viruses · 2021Article
- 4,7-Disubstituted 7Molecules (Basel, Switzerland) · 2021Article
- Review
- Comparison of Multiple Bioactive Constituents in the Corolla and Other Parts ofMolecules (Basel, Switzerland) · 2021Article
- Products of Oxidative Guanine Damage Form Base Pairs with Guanine.International journal of molecular sciences · 2020Review
- Current and Promising Antivirals Against Chikungunya Virus.Frontiers in public health · 2020Review
- Synergistic lethal mutagenesis of hepatitis C virus.Antimicrobial agents and chemotherapy · 2019Article
- Lethal Mutagenesis of Rift Valley Fever Virus Induced by Favipiravir.Antimicrobial agents and chemotherapy · 2019Article
- Contribution of a Multifunctional Polymerase Region of Foot-and-Mouth Disease Virus to Lethal Mutagenesis.Journal of virology · 2018Article
- Rare haplotype load as marker for lethal mutagenesis.PloS one · 2018Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue virus affects millions of people worldwide each year. To date, there is no drug for the treatment of dengue-associated disease. Nucleosides are effective antivirals and work by inhibiting the accurate replication of the viral genome. Nucleobases offer a cheaper alternative to nucleosides for broad antiviral applications. Metabolic activation of nucleobases involves condensation with 5-phosphoribosyl-1-pyrophosphate to give the corresponding nucleoside-5'-monophosphate. This could provide an alternative to phosphorylation of a nucleoside, a step that is often rate limiting and inefficient in activation of nucleosides. We evaluated more than 30 nucleobases and corresponding nucleosides for their antiviral activity against dengue virus. Five nucleobases and two nucleosides were found to induce potent antiviral effects not previously described. Our studies further revealed that nucleobases were usually more active with a better tissue culture therapeutic index than their corresponding nucleosides. The development of viral lethal mutagenesis, an antiviral approach that takes into account the quasispecies behavior of RNA viruses, represents an exciting prospect not yet studied in the context of dengue replication. Passage of the virus in the presence of the nucleobase 3a (T-1105) and corresponding nucleoside 3b (T-1106), favipiravir derivatives, induced an increase in apparent mutations, indicating lethal mutagenesis as a possible antiviral mechanism. A more concerted and widespread screening of nucleobase libraries is a very promising approach to identify dengue virus inhibitors including those that may act as viral mutagens.
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