Mechanism of nrti

NRTIs are analogs of native ribosides (nucleosides or nucleotides containing ribose), which all lack a 3’-hydroxyl group. Once they enter cells, they are phosphorylated by a variety of cellular enzymes to the corresponding triphosphate analog, which is preferentially incorporated into the viral DNA by virus reverse transcriptase. Because the 3’-hydroxyl group is not present, a 3’-5’ phosphodiester bond between an incoming nucleoside triphosphate and the growing DNA chain cannot be formed, and DNA chain elongation is terminated. Affinities of the drugs for many host cell DNA polymerases are lower than they are for HIV reverse transcriptase, mitochondrial DNA polymerase γ appears to be susceptible at therapeutic concentrations.