Favipiravir

Biological Activity

Favipiravir (T-705) is a potent and selective RNA-dependent RNA polymerase inhibitor, used to treat influenza virus infections. Its active form, Favipiravir-ribofuranosyl-5′-triphosphate (RTP) inhibits the influenza viral RNA-dependent RNA polymerase (RdRP) activity with an IC50 of 341 nM. Favipiravir shows anti-influenza virus activities with IC50 ranged from 0.013 to 0.48 μg/ml for the influenza A viruses, from 0.039 to 0.089 μg/ml for the influenza B viruses, and from 0.030 to 0.057 μg/ml for the influenza C viruses. In mammalian cell lines (MDCK cells, Vero cells, HEL cells, A549 cells, HeLa cells, and HEp-2 cells), Favipiravir shows no cytotoxicity at concentrations up to 1,000 μg/ml. In MDCK cells inoculated with seasonal influenza A (H1N1) viruses, Favipiravir induces lethal mutagenesis.

Protocol (for reference only)

Cell Experiment
Cell lines	MDCK cells, Vero cells, HEL cells, A549 cells, HeLa cells, and HEp-2 cells
Preparation method	The cytotoxicity of T-705 is evaluated by an assay with XTT. XTT is converted to aqueous formazan by an enzyme in MDCK cells, Vero cells, HEL cells, A549 cells, HeLa cells, and HEp-2 cells. The compounds are diluted to the appropriate concentrations (volume, 100 μl) with test medium (EMEM containing 10% FCS) in 96-well culture plates in which each well contains a concentration of 2 × 103 cells/100 μL. The test plates are incubated for 3 days at 37°C in 100% humidity and 5% CO2. After 3 days, 50 μl of the XTT reagent (1 mg/ml in FCS-free EMEM containing 5 mM phenazine methosulfate) is added, and the reaction product is assayed by measurement of the absorbance at 450 nm with a microplate reader. Cytotoxicity is expressed as the 50% cell-inhibitory concentration (CC50).
Concentrations	1000 μg/mL
Incubation time	3 d

Animal Experiment
Animal models	Mice infected with influenza virus A/PR/8/34
Formulation	0.5% methylcellulose
Dosages	200 mg/kg/day
Administration	p.o.

Chemical Information

Molecular Weight	157.1
Formula	C5H4FN3O2
CAS Number	259793-96-9
Solubility (25°C)	DMSO 50 mg/mL Water 5 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

References

[1] Oestereich L, et al. Antiviral Res. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model.

[2] Smither SJ, et al. Antiviral Res. Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model.