Types
RTIs come in three forms:
- Nucleoside analog reverse-transcriptase inhibitors (NARTIs or NRTIs)
- Nucleotide analog reverse-transcriptase inhibitors (NtARTIs or NtRTIs)
- Non-nucleoside reverse-transcriptase inhibitors (NNRTIs)
The mode of action of NRTIs and NtRTIs is essentially the same; they are analogues of the naturally occurring deoxynucleotides needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain. However, unlike the natural deoxynucleotides substrates, NRTIs and NtRTIs lack a 3'-hydroxyl group on the deoxyribose moiety. As a result, following incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as chain termination. All NRTIs and NtRTIs are classified as competitive substrate inhibitors.
In contrast, NNRTIs have a completely different mode of action. NNRTIs block reverse transcriptase by binding at a different site on the enzyme, compared to NRTIs and NtRTIs. NNRTIs are not incorporated into the viral DNA but instead inhibit the movement of protein domains of reverse transcriptase that are needed to carry out the process of DNA synthesis. NNRTIs are therefore classified as non-competitive inhibitors of reverse transcriptase.
Read more about this topic: Reverse-transcriptase Inhibitor
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