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A **combination regimen** of four direct-acting antivirals—**samatasvir** (IDX719, an HCV NS5A inhibitor), **simeprevir** (an HCV NS3/4A protease inhibitor), **TMC647055** (an HCV NS5B non-nucleoside inhibitor), and **ritonavir** (a CYP3A4 inhibitor used as a pharmacokinetic booster)—investigated in phase 2 clinical trials for the treatment of chronic **hepatitis C virus (HCV) infection** in adults, including genotype 1a and 1b patients. - **Samatasvir** blocks the HCV NS5A protein, disrupting viral RNA replication. - **Simeprevir** inhibits the HCV NS3/4A protease, blocking viral polyprotein maturation. - **TMC647055** binds to the NS5B polymerase (NNI-1 pocket), hindering viral RNA synthesis. - **Ritonavir**, though not active against HCV, boosts exposure of co-administered agents through CYP3A4 inhibition. Regimens with and without ribavirin were evaluated. The combination aimed to achieve sustained virologic response (SVR12) and was generally well tolerated in clinical studies[2][3][4][1][5].
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