Tenofovirdiphosphate is an inhibitor of HIV reverse transcriptase (Kis = 0.022 and 1.55 μM for RNA and DNA, respectively) and hepatitis B virus (HBV) polymerase (Ki = 0.18 μM). It is selective for these enzymes over DNA polymerase α and β, as well as mitochondrial DNA polymerase γ (Kis = 5.2, 81.7, and 59.5 μM, respectively). Tenofovirdiphosphate is formed intracellularly through phosphorylation of the prodrugs tenofovir and tenofovir disoproxil by nucleotide kinases. Increased levels of tenofovirdiphosphate in isolated peripheral blood mononuclear cells (PBMCs) correlate with a decrease in the risk of simian HIV (SHIV) acquisition in a macaque model of rectal SHIV transmission.
Tenofovirdiphosphate (TFV-DP) is a competitive inhibitor of DNA polymerases, specifically targeting dATP, and it serves as a substrate for the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1)[1].