ArticleAntimicrobial agents and chemotherapy2016
Distinct Effects of T-705 (Favipiravir) and Ribavirin on Influenza Virus Replication and Viral RNA Synthesis.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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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
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
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.
- A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval.Drug design, development and therapy · 2022Pooled it
- An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics.Journal of infection and public health · 2020Pooled it
- Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2023Trial
- Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome.Signal transduction and targeted therapy · 2021Trial
- Influenza A deletion-containing viral genome production is altered by metabolites, metabolic signaling molecules, and cyanobacterial extracts.Applied and environmental microbiology · 2026Article
- Review on drug repositioning of some FDA-approved drugs for treatment of cancer/microbial diseases.RSC advances · 2026Review
- A scoping review of influenza RdRp-targeting inhibitors: mechanisms, clinical translation, and emerging challenges.Frontiers in microbiology · 2026Review
- Article
- Favipiravir as a potent inhibitor of Newcastle disease virus:Veterinary world · 2025Article
- Advances in the Treatment of Enterovirus-D68 and Rhinovirus Respiratory Infections.Infectious disease reports · 2025Review
- Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies.Molecules (Basel, Switzerland) · 2024Review
- N4-Hydroxycytidine/molnupiravir inhibits RNA virus-induced encephalitis by producing less fit mutated viruses.PLoS pathogens · 2024Article
- Article
- Pharmacogenomic Studies of Antiviral Drug Favipiravir.Pharmaceutics · 2024Article
- Favipiravir induces HuNoV viral mutagenesis and infectivity loss with clinical improvement in immunocompromised patients.Clinical immunology (Orlando, Fla.) · 2024Article
- Crimean-Congo haemorrhagic fever virus.Nature reviews. Microbiology · 2023Review
- Insights into targeting SARS-CoV-2: design, synthesis,RSC medicinal chemistry · 2023Article
- Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity.Microorganisms · 2023Article
- Maximal interferon induction by influenza lacking NS1 is infrequent owing to requirements for replication and export.PLoS pathogens · 2023Article
- Current understanding of nucleoside analogs inhibiting the SARS-CoV-2 RNA-dependent RNA polymerase.Computational and structural biotechnology journal · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-705 (favipiravir) is a new antiviral agent in advanced clinical development for influenza therapy. It is supposed to act as an alternative substrate for the viral polymerase, causing inhibition of viral RNA synthesis or virus mutagenesis. These mechanisms were also proposed for ribavirin, an established and broad antiviral drug that shares structural similarity with T-705. We here performed a comparative analysis of the effects of T-705 and ribavirin on influenza virus and host cell functions. Influenza virus-infected cell cultures were exposed to T-705 or ribavirin during single or serial virus passaging. The effects on viral RNA synthesis and infectious virus yield were determined and mutations appearing in the viral genome were detected by whole-genome virus sequencing. In addition, the cellular nucleotide pools as well as direct inhibition of the viral polymerase enzyme were quantified. We demonstrate that the anti-influenza virus effect of ribavirin is based on IMP dehydrogenase inhibition, which results in fast and profound GTP depletion and an imbalance in the nucleotide pools. In contrast, T-705 acts as a potent and GTP-competitive inhibitor of the viral polymerase. In infected cells, viral RNA synthesis is completely inhibited by T-705 or ribavirin at ≥50 μM, whereas exposure to lower drug concentrations induces formation of noninfectious particles and accumulation of random point mutations in the viral genome. This mutagenic effect is 2-fold higher for T-705 than for ribavirin. Hence, T-705 and ribavirin both act as purine pseudobases but profoundly differ with regard to the mechanism behind their antiviral and mutagenic effects on influenza virus.
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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.