Filibuvir

Filibuvir is an orally active, selective non-nucleoside inhibitor of the HCV nonstructural 5B protein (NS5B) RNA-dependent RNA polymerase (RdRp). Filibuvir binds noncovalently in the thumb II allosteric pocket of NS5B. Filibuvir inhibits genotype 1a and 1b replicons with EC₅₀s of 59 nM for both isoforms, respectively^[1]. Filibuvir preferentially inhibits elongative RNA synthesis and potently decreases viral RNA accumulation^[2]. In Vitro: Filibuvir (0.01-10000 nM; 48 h) inhibits the WT 1b replicon in a dose-dependent manner, with an EC₅₀ of ∼70 nM in Huh7.5 cells harboring the HCV replicon. Filibuvir binds to the HCV polymerase with a dissociation constant of 29 nM^[2].
Filibuvir preferentially inhibits elongative RNA synthesis rather than de novo-initiated RNA synthesis. Filibuvir has no obvious effect on de novo-initiated RNA synthesis (IC₅₀=∼5 μM) but decreases primer extension from PE46, with an IC₅₀ of 73 nM^[2].