Mechanism of action<unk>  inhibits the hepatitis C NS5B protein.<unk>  appears to have a high barrier to the development of resistance.<unk>  is a prodrug of the Protide type, whereby the active phosphorylated nucleotide is granted cell permeability and oral bioavailability. It is metabolized to the active antiviral agent GS-461203 (2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-triphosphate). GS-461203 serves as a defective substrate for the NS5B protein, which is the viral RNA polymerase, thus acts as an inhibitor of viral RNA synthesis. Although<unk>  has a 3' hydroxyl group to act as a nucleophile for an incoming NTP, a similar nucleotide analogue, 2'-deoxy-2'-α-fluoro-β-C-methylcytidine, is proposed to act as a chain terminator because the 2' methyl group of the nucleotide analogue causes a steric clash with an incoming NTP.<unk>  would act in a similar way. Pharmacokinetics<unk>  is only administered orally. The peak concentration after oral administration is 0.5–2 hours post-dose, regardless of initial dose. Peak plasma concentration of the main circulating metabolite GS-331077 occurs 2–4 hours post-dose. GS-331077 is the pharmacologically inactive nucleoside. Plasma protein binding of<unk>  is 61–65%, while GS-331077 has minimal binding.<unk>  is activated in the liver to the triphosphate GS-461203 by hydrolysis of the carboxylate ester by either of the enzymes cathepsin A or carboxylesterase 1, followed by cleaving of the phosphoramidate by the enzyme histidine triad nucleotide-binding protein 1 (HINT1), and subsequent repeated phosphorylation. Dephosphorylation creates the inactive metabolite GS-331077. The half life of<unk>  is 0.4 hours, and the half life of GS-331077 is 27 hours. Following a single 400 mg oral dose of<unk> , 80% is excreted in urine, 14% in feces, and 2.5% in expired air recovery. However, of the urine recovery 78% was the metabolite (GS-331077) and 3.5% was<unk> .
Sofosbuvir
Dasabuvir
Telaprevir
Fosamprenavir
Enfuvirtide
Coronavir
Abacavir
Indinavir