Ziresovir

Ziresovir (AK0529;RO-0529) is a potent, selective, and orally bioavailable respiratory syncytial virus (RSV) fusion (F) protein (RSV F) protein inhibitor. Ziresovir shows anti-RSV activity (EC₅₀=3 nM) and highlights pharmacokinetics in animal species^[1]. IC50 & Target: RSV F protein (respiratory syncytial virus fusion protein)^[1] EC50: 3 nM (RSV F)^[1] In Vitro: Ziresovir shows different efficacy in Wild Type (WT) and Mutant Strains RSV with EC₅₀/EC₉₀ values (μM) of 0.003/0.005 (WT), 2.1/10.0 (D486N), and >10/>10 (D489A), respectively^[1].
RO-0529 (100 nM; 4 d) inhibits RSV F protein-induced cell-cell fusion process, and suppresses the syncytia formation induced by the RSV F protein^[1].
In Vivo: Ziresovir (12.5 mg/kg, 50 mg/kg; p.o.; twice daily; 4 d) results reduction of RSV titer in mouse lung^[1].
Ziresovir (10 mg/kg; p.o.; single dose) exhibits good oral exposure and bioavailability?with F(%) of 32% in male Wistar-Han rats^[1].
Ziresovir (150 mg/kg; p.o.; single dose) demonstrates a high tissue distribution to lung than plasma in CD-1 Mice^[1].
Pharmacokinetics of Ziresovir in male Wistar-Han rats^[1]

Dose (mg/kg)	AUC0-24h(p.o.) (ng·h/mL)	CL (mL/min/kg)	T1/2(i.v.) (h)	Vss (L/kg)	F (%)
2 mg/kg (iv) or 10 mg/kg (po)	906	58	1.2	3.9	32

Pharmacokinetics of Ziresovir in CD-1 Mice^[1]

Dose (mg/kg)	AUC0-24h(p.o.) (μg·h/L)	tissue/lasma AUC0-24h ratio (μg·h/L)	T1/2 (h)	Tmax (h)	Cmax (μg/L)
plasma	8,380	1	1.02	0.25	5090
lung	72,400	8.6	3.31	1	22700