Human immunodeficiency virus 1 reverse transcriptase (HIV-1 RT) (HIV-1 RT)

Human immunodeficiency virus 1 reverse transcriptase (HIV-1 RT) is a multifunctional viral enzyme that is essential for the replication of HIV-1, the causative agent of AIDS [2, 15, 19]. It is a heterodimer composed of two subunits, p66 and p51, which together provide the enzymatic activities required to convert the single-stranded viral RNA genome into double-stranded DNA [3, 15, 17]. This conversion process involves three sequential biochemical activities: RNA-dependent DNA polymerase activity, ribonuclease H (RNase H) activity to degrade the RNA template, and DNA-dependent DNA polymerase activity to synthesize the second DNA strand [5, 18]. Because reverse transcription is a defining and indispensable step in the retroviral life cycle, HIV-1 RT has become one of the most important targets for antiretroviral therapy [7, 11]. Therapeutic agents targeting this enzyme are broadly classified into nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) [11, 12]. NRTIs function as competitive inhibitors that incorporate into the growing DNA chain and cause premature chain termination, while NNRTIs bind to an allosteric site to inhibit the polymerase activity non-competitively [11]. Despite the success of these drugs in transforming HIV into a manageable chronic condition, the high error rate of HIV-1 RT leads to frequent mutations [4, 6]. These mutations often result in the emergence of drug-resistant viral strains, necessitating the continuous development of new inhibitors and complex multi-drug regimens to maintain viral suppression [10, 14].

Other names

RNA-directed DNA polymerasep66/p51 heterodimerPolHIV RTReverse transcriptase

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) act as competitive inhibitors and chain terminators by lacking a 3'-hydroxyl group [11, 12]. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) bind to an allosteric pocket near the polymerase active site, causing a conformational change that inhibits the enzyme's activity [11].