Related Experiment Video
Updated: Oct 1, 2025
Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
Anti-influenza Virus Activity of Methylthio-Formycin Distinct From That of T-705
Naoki Takizawa1, Hisashi Takada1, Maya Umekita1
1Institute of Microbial Chemistry (BIKAKEN), Tokyo, Japan.
Abstract:
Seasonal influenza virus epidemics result in severe illness, and occasionally influenza pandemics cause significant morbidity and mortality, although vaccines and anti-influenza virus drugs are available. By screening an in-house library, we identified methylthio-formycin (SMeFM), an adenosine analog, as a potent inhibitor of influenza virus propagation. SMeFM inhibited the propagation of influenza A and B viruses (IC50: 34.1 and 37.9 nM, respectively) and viruses showing reduced susceptibility to baloxavir and neuraminidase inhibitors but not T-705 (Favipiravir). However, the combination of T-705 and SMeFM inhibited the propagation of the influenza virus not in an antagonistic but in a slightly synergistic manner, suggesting that SMeFM has targets distinct from that of T-705. SMeFM induced A-to-C transversion mutations in virus genome RNA, and SMeFM triphosphate did not inhibit in vitro viral RNA synthesis. Our results show that SMeFM inhibits the propagation of the influenza virus by a mechanism different from that of T-705 and is a potential drug candidate to develop for anti-influenza drug.
Insights
Methylthio-formycin (SMeFM) effectively inhibits influenza A and B virus propagation. This novel adenosine analog shows potential as an anti-influenza drug, working through a distinct mechanism compared to existing treatments.
Area of Science:
- Virology
- Drug Discovery
- Molecular Biology
Background:
- Seasonal influenza epidemics and pandemics cause significant global morbidity and mortality.
- Existing vaccines and anti-influenza drugs face challenges with resistance and efficacy.
- Novel therapeutic strategies are crucial for combating influenza virus infections.
Purpose of the Study:
- To identify novel inhibitors of influenza virus propagation.
- To characterize the mechanism of action of identified compounds.
- To evaluate the potential of new drug candidates against influenza.
Main Methods:
- Screening of an in-house chemical library to identify inhibitors.
- Antiviral assays to determine inhibitory concentrations (IC50) against influenza A and B viruses.
- Resistance profiling against existing antiviral drugs (baloxavir, neuraminidase inhibitors, T-705).
- Mutation analysis of viral genome RNA and in vitro RNA synthesis assays.
Main Results:
- Methylthio-formycin (SMeFM), an adenosine analog, was identified as a potent inhibitor of influenza A and B virus propagation (IC50 values in nanomolar range).
- SMeFM demonstrated efficacy against influenza viruses resistant to baloxavir and neuraminidase inhibitors, but not T-705 (Favipiravir).
- Combination therapy with T-705 showed slight synergy, indicating distinct mechanisms of action.
- SMeFM induced A-to-C transversion mutations in the viral genome and did not inhibit in vitro viral RNA synthesis.
Conclusions:
- SMeFM is a potent inhibitor of influenza virus propagation with a novel mechanism of action distinct from T-705.
- SMeFM exhibits activity against drug-resistant influenza strains.
- SMeFM represents a promising drug candidate for the development of new anti-influenza therapies.
More Related Videos
07:50Author Spotlight: Scalable Drug Screening Protocol for Efficient Discovery of M. abscessus Treatments
Published on: October 25, 2024
09:31Fluorescence-based Neuraminidase Inhibition Assay to Assess the Susceptibility of Influenza Viruses to The Neuraminidase Inhibitor Class of Antivirals
Published on: April 15, 2017
