AVL-192

AVL-192 is a preclinical, orally available small-molecule hepatitis C virus (HCV) protease inhibitor designed by Avila Therapeutics using a targeted covalent drug platform. It selectively and irreversibly inhibits the viral NS3/4A serine protease by covalently bonding to a noncatalytic cysteine (Cys159) in the substrate-binding site, which is structurally unique to the viral protease and absent from host proteases, thereby achieving high potency while minimizing off-target effects.[1][12][3] Preclinical studies show that AVL-192 potently inhibits wild-type NS3/4A as well as clinically observed drug‑resistant NS3 variants across multiple HCV genotypes, exhibits prolonged target inhibition after compound removal, and demonstrates high plasma exposure and oral bioavailability in animal models, supporting its potential as a once‑daily, pan‑genotypic HCV therapy.[1][5][13]