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Reverse transcriptase of human immunodeficiency virus (HIV-1 RT) is a multifunctional enzyme central to HIV replication, converting the single-stranded viral RNA genome into double-stranded DNA for integration into the host genome. It is a heterodimer (p66/p51) with two primary enzymatic activities: polymerase (both RNA- and DNA-dependent) and ribonuclease H, which degrades the RNA strand of RNA/DNA hybrids formed during replication. This enzyme is essential for viral proliferation and a principal target of antiretroviral drugs; over half of approved HIV therapies target its activity, either by inhibiting the DNA polymerization process (NRTIs, NNRTIs) or interfering with RNA cleavage. Its structural and functional features, combined with high mutation rates, make it a significant focus for ongoing drug development and resistance monitoring.
Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): Incorporate into viral DNA chain, terminate DNA elongation. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): Allosterically inhibit polymerase activity by binding to NNRTI pocket. RNase H inhibitors (experimental): Block RNA degradation during reverse transcription.
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