ArticleChemistry (Weinheim an der Bergstrasse, Germany)2026
Membrane-Permeable Nucleoside T-1106 Diphosphate and Triphosphate Analogues as Antiviral Pronucleotides.
Article in Chemistry (Weinheim an der Bergstrasse, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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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
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Who cites it
2 citing papers in PubMed.
- Triphosphate and diphosphate nucleoside prodrugs: broadening the therapeutic potential of nucleoside-based treatments.RSC medicinal chemistry · 2026Review
- Membrane-Permeable Nucleoside T-1106 Diphosphate and Triphosphate Analogues as Antiviral Pronucleotides.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
The nucleobase T-1105, the non-fluorinated analogue of favipiravir (T-705), inhibits viral RNA synthesis after conversion to its ribonucleoside-5'-triphosphate (T-1105-RTP) metabolite. However, this metabolic activation is rate-limiting and inefficient. We here report the chemical synthesis and evaluation of three series of T-1105-ribonucleoside (T-1106)-DiPPro- and TriPPPro-nucleotide prodrugs to allow their cellular uptake. Their efficient release of the T-1106-diphosphate and triphosphate forms was demonstrated upon incubation in PBS, pig liver esterase, extract of human T-lymphoblast CEM/0 cells and human plasma. This validates the successful hydrolysis and delivery of the corresponding nucleotides, via chemical or enzyme-triggered mechanisms. Interestingly, several T-1106-DiPPro-prodrugs, for example, compound 24h, and TriPPPro-prodrugs proved superior to the parent T-1106 nucleoside, in inhibiting influenza A and influenza B replication in MDCK cells, and of human coronavirus OC43 in HEL299 cells. This validates the utility of our pronucleotide strategy to overcome the inefficient activation of T-1106 and increase the antiviral efficacy against influenza and coronaviruses.
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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.