Human immunodeficiency virus 1 ribonuclease H (RNase H)

Human immunodeficiency virus 1 ribonuclease H (HIV-1 RNase H) is a catalytic domain of the viral reverse transcriptase (RT) enzyme, essential for the replication of HIV-1 [2, 10]. Its primary biological function is to degrade the RNA strand of the RNA-DNA hybrid intermediate formed during the conversion of the single-stranded viral RNA genome into double-stranded DNA [3, 5]. This activity is crucial for several steps of reverse transcription, including the removal of the tRNA primer and the processing of the polypurine tract (PPT) [2, 11]. While the polymerase activity of RT is the target of many FDA-approved antiretroviral drugs, no approved therapies currently target the RNase H domain specifically [1, 9]. Experimental inhibitors, such as β-thujaplicinol and GSK5750, typically act by chelating divalent metal ions (Mg2+ or Mn2+) within the enzyme's active site to block catalysis [2, 16]. Development of these inhibitors faces significant challenges, including the shallow topography of the active site and the risk of off-target toxicity due to structural similarities with human RNase H enzymes [5, 16].

Other names

HIV-1 RNase HReverse transcriptase-associated ribonuclease HRT-associated RNase HRNase H domain of HIV-1 RT

Inhibition of the ribonuclease H activity of reverse transcriptase, typically through chelation of divalent metal ions (Mg2+ or Mn2+) in the active site, preventing the degradation of the viral RNA template during DNA synthesis [2, 3, 5].