Transformations suffered by sofosbuvir in the liver:

• Isopropyl ester hydrolisis. Catalised by catepsin A (CatA) or carboxylesterase 1 (CES1).
• Release of phenol group attached to phosphate, by internal nucleophilic attack of carboxylate to phosphate. A spontaneous reaction.
• Deamination, releasing alanine. Catalised by Hint1.
• Phosphorilation to diphosphate. Catalised by UMP-CMP kinase.
• Phosphorilation to triphosphate. Catalised by nucleoside diphosphate kinase.

Triphosphate is the active drug, a potent inhibitor of NS5B, the RNA polymerase in HCV virus. Being a structural analogye of UTP (the substrate) allows it to bind the catalytic centre of NS5B.

Figure reproduced according to conditions set by the publisher.