The drug zidovudine is an example of a

• A. Nonnucleoside reverse-transcriptase inhibitor.
• B. Protease inhibitor.
• C. Fusion inhibitor.
• D. Nucleoside analogue reverse-transcriptase inhibitor.

Answer: (D)

Zidovudine is a nucleoside analogue reverse-transcriptase inhibitor. It must be activated inside the cell by kinases to zidovudine triphosphate, which then competes with thymidine triphosphate for incorporation by HIV reverse transcriptase. Once incorporated into the viral DNA, it lacks a 3' hydroxyl group, so no additional nucleotides can be added, and DNA synthesis stops. This chain-termination mechanism is what defines NRTIs. It differs from non-nucleoside RT inhibitors, which bind reverse transcriptase at a separate site without needing phosphorylation, and from protease inhibitors or fusion inhibitors, which target entirely different steps in the HIV life cycle.