Human immunodeficiency virus type 1 reverse transcriptase ribonuclease H (HIV-1 RNase H)

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a multifunctional enzyme essential for converting the viral single-stranded RNA genome into double-stranded DNA (dsDNA) for integration into the host genome (UniProt P03366). The RNase H activity, located in the C-terminal domain of the p66 subunit, specifically catalyzes the degradation of the RNA template from the RNA:DNA hybrid intermediate formed during reverse transcription (PubMed PMID: 22403118). This degradation is a prerequisite for the synthesis of the second DNA strand and the generation of the polypurine tract (PPT) primer. While the polymerase activity of RT is the target of many FDA-approved drugs, the RNase H domain remains an unexploited therapeutic target with no approved inhibitors to date (PubMed PMID: 30245458). Inhibiting RNase H activity effectively halts viral replication by preventing the completion of the reverse transcription process. Experimental inhibitors often target the highly conserved active site by chelating essential magnesium ions or by binding to allosteric sites that disrupt the enzyme's conformational dynamics (PubMed PMID: 29134344).

Other names

HIV-1 RT RNase HRibonuclease H domain of HIV-1 reverse transcriptasep15 domain of HIV-1 RTHIV-1 RT RNase H activity

Inhibition of the ribonuclease H activity of HIV-1 reverse transcriptase, preventing the degradation of the viral RNA template from the RNA:DNA hybrid intermediate, which halts the synthesis of double-stranded viral DNA (PubMed PMID: 22403118).