Tenofovir is a nucleotide analog that has shown to be effective against HIV, herpes simplex virus-2, and hepatitis B virus. When HIV 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 HIV viruses bud from the cell. Tenofovir enters the cell via solute carrier family 22 member 8 and is converted into tenofovir monophosphate by adenylate kinase. Nucleoside diphosphate kinase then converts tenofovir monophosphate into tenofovir diphosphate. Tenofovir diphosphate is an analog of deoxyadenosine triphosphate (dATP). Tenofovir diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dATP and by incorporation into viral DNA. Tenofovir diphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once tenofovir 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.

Tenofovir Pathway (New) References