HIV-1 Reverse Transcriptase Still Remains a New Drug Target: Structure, Function, Classical Inhibitors, and New Inhibitors with Innovative Mechanisms of Actions

Figure 4

Amino acid residues involved in RTI binding. RT two subunits are in green (p66) and in gray (p51). The catalytic residues of the polymerase active site and the RNase H active site are colored in yellow. NRTIs and NtRTIs interact with residues close to the polymerase active site (blue). NNRTIs bind in a hydrophobic pocket next to the polymerase active site (magenta). RHRTIs such as DKAs, N-hydroxyimides, N-hydroxy quinazolinediones and naphthyridine derivatives bind in the RNase H active site (in yellow on the right). Vinylogous ureas bind to a hydrophobic pocket at the interface between the RNase H domain and the p51 subunit (cyan). Hydrazone derivatives have been proposed to bind two different sites (red). One located between the polymerase active site and the NNRTI-binding pocket (sharing a few residues with it) and the second one located between the RNase H and the connection domain. Anthraquinone derivatives have been proposed to bind to the first hydrazone pocket next to the NNRTI-binding site.