at-527 + daclatasvir

AT-527 + daclatasvir is an **oral combination therapy** of two antiviral agents: **AT-527**, a double prodrug of a guanosine nucleotide analog developed to inhibit viral RNA-dependent RNA polymerase (RdRp), and **daclatasvir**, an approved inhibitor of the hepatitis C virus (HCV) NS5A protein. AT-527 is metabolized in human cells to its active triphosphate form, AT-9010, which inhibits viral replication by targeting the RdRp (NS5B) and also the NiRAN domain of nsp12, impairing both RNA synthesis and viral protein priming[1][2][4][5]. Daclatasvir directly blocks HCV replication by binding to NS5A, a viral phosphoprotein required for replication and assembly. The combination was studied primarily for the treatment of chronic hepatitis C infection, where phase 2 trials demonstrated high rates of sustained virologic response (SVR) and good tolerability[1][3][4].