Structural basis of HIV inhibition by L-nucleosides: Opportunities for drug development and repurposing.

Infection with HIV can cripple the immune system and lead to AIDS. Hepatitis B virus (HBV) is a hepadnavirus that causes human liver diseases. Both pathogens are major public health problems affecting millions of people worldwide.

HIV Reverse Transcriptase Pre-Steady-State Kinetic Analysis of Chain Terminators and Translocation Inhibitors Reveals Interactions between Magnesium and Nucleotide 3'-OH.

Deoxythymidine triphosphate analogues with various 3' substituents in the sugar ring (-OH (dTTP)), -H, -N, -NH, -F, -O-CH, no group (2',3'-didehydro-2',3'-dideoxythymidine triphosphate (d4TTP)), and those retaining the 3'-OH but with 4' additions (4'--methyl, 4'--ethyl) or sugar ring modifications (d-carba dTTP) were evaluated using pre-steady-state kinetics in low (0.5 mM) and high (6 mM) Mg with HIV reverse transcriptase (RT). Analogues showed diminished observed incorporation rate constants ( ) compared to dTTP ranging from about 2-fold (3'-H, -N, and d4TTP with high Mg) to >10-fold (3'-NH and 3'-F with low Mg), while 3'-O-CH dTTP incorporated much slower than other analogues.