How do NNRTIs differ in mechanism from NRTIs?

How do NNRTIs differ in mechanism from NRTIs?

• A. NNRTIs inhibit integrase; NRTIs inhibit protease.
• B. NNRTIs increase mutation rate; NRTIs repair DNA.
• C. NNRTIs bind non-competitive to reverse transcriptase, while NRTIs are nucleoside analogs that terminate DNA chain elongation after phosphorylation.
• D. NNRTIs block entry; NRTIs block fusion.

Answer: (C)

NNRTIs and NRTIs both target reverse transcriptase, but they do so in different ways. NNRTIs bind to a specific pocket on reverse transcriptase and inhibit its activity through a noncompetitive mechanism—binding alters the enzyme’s shape so it can’t synthesize DNA efficiently, and they are not incorporated into the viral DNA. In contrast, NRTIs are nucleoside or nucleotide analogs that must be phosphorylated inside the cell to become active. Once activated, they compete with natural nucleotides and are incorporated into the growing DNA chain during reverse transcription, but they lack a 3' hydroxyl group, causing immediate chain termination and stopping DNA synthesis. Thus, NNRTIs block RT activity by changing the enzyme’s shape, while NRTIs act as substrate analogs that terminate DNA elongation after incorporation.

NNRTIs and NRTIs both target reverse transcriptase, but they do so in different ways. NNRTIs bind to a specific pocket on reverse transcriptase and inhibit its activity through a noncompetitive mechanism—binding alters the enzyme’s shape so it can’t synthesize DNA efficiently, and they are not incorporated into the viral DNA. In contrast, NRTIs are nucleoside or nucleotide analogs that must be phosphorylated inside the cell to become active. Once activated, they compete with natural nucleotides and are incorporated into the growing DNA chain during reverse transcription, but they lack a 3' hydroxyl group, causing immediate chain termination and stopping DNA synthesis. Thus, NNRTIs block RT activity by changing the enzyme’s shape, while NRTIs act as substrate analogs that terminate DNA elongation after incorporation.