AVL-181

AVL-181 is an orally available, covalent small-molecule inhibitor of the hepatitis C virus (HCV) NS3/4A serine protease, developed by Avila Therapeutics as a pan-genotypic direct-acting antiviral for chronic HCV infection.[1][5][7][11] Designed using Avila’s targeted covalent drug platform, it forms a highly specific, irreversible covalent bond with a noncatalytic cysteine in the NS3/4A protease, completely inactivating proteolytic activity and “silencing” this essential viral protein across multiple HCV genotypes and clinically described drug‑resistant mutant proteases.[1][5][7][11] Preclinical data showed potent inhibition of wild-type and resistant NS3/4A variants, prolonged inhibition of protease activity in cell-based replicon systems for more than 48 hours after brief exposure, sustained target occupancy and protease suppression in a mouse liver NS3/4A expression model for at least 10 hours after a single dose, and complete in vitro viral RNA clearance when combined with a non‑nucleoside HCV polymerase inhibitor.[1][3][5][7] AVL-181 was advanced as a clinical candidate for once-daily oral therapy in combination regimens for HCV, but public information describes only preclinical development.