Adefovir dipivoxil is a nucleotide analog used to treat chronic hepatitis B virus (HBV). When HBV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HBV viruses bud from the cell. Adefovir dipivoxil enters the cell and is metabolized to release adefovir by carboxylesterase enzyme. Adefovir is converted into adefovir monophosphate by adenylate kinases. Nucleoside diphosphate kinases then convert adefovir monophosphate into adefovir diphosphate. Adefovir diphosphate is an analog of deoxyadenosine-5'-triphosphate (dATP). Adefovir diphosphate inhibits the activity of HBV reverse transcriptase by competing with its substrate, dATP and by incorporation into viral DNA. Adefovir diphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once adefovir diphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed.

Adefovir Dipivoxil Pathway (New) References