AVG-233

AVG-233 is a potent, orally active RNA dependent RNA polymerase (RdRp) inhibitor. AVG-233 prevents initiation of the viral polymerase complex at the promoter. AVG-233 binding site is present in the L_1-1749 fragment. AVG-233 has nanomolar activity against both RSV strains and clinical RSV isolates (EC₅₀=0.14-0.31 μM). AVG-233 can be used for research of respiratory syncytial virus (RSV)^[1][2]. In Vitro:AVG-233 (1-100 μM) blocks 3´RNA extension elongation but does not interfere with 3´RNA extension by up to three nucleotides after de novo initiation from the promoter or back-priming^[1].
AVG-233 (20 μM) reduces virus yield of RSV A2-L19F (EC₅₀=0.31 μM), RSV strain 2-20 (EC₅₀=0.14 μM) and RSV clinical isolate 718 (EC₅₀=0.2 μM) ^[1].
AVG-233 (1.25-40 μM; 0-300 s) suppresses RNA synthesis by the L1-1749 fragment in a dose-dependent manner with an IC₅₀ value of 13.7 μM. AVG-233 bounds L and the L_1-1749 fragment with similar affinities (dissociation constants (KD’s) are 38.3 μM and 53.1 μM, respectively)^[2].
In Vivo:AVG-233 (50-100 mg/kg; i.g.; once) decreases lung viral load in the RSV mouse model^[2].
AVG-233 (2-20 mg/kg; i.v. and p.o.; once; male CD-1 mice) has good orally bioavailable and the maximum plasma concentration about 2 μM^[1].