Past and Future. Current Drugs Targeting HIV-1 Integrase and Reverse Transcriptase-Associated Ribonuclease H Activity: Single and Dual Active Site Inhibitors

Abstract

Catalytic HIV type-1 (HIV-1) integrase (IN) and ribonuclease H (RNase H) domains belong to the polynucleotidyl transferase superfamily and are characterized by highly conserved motifs that coordinate two divalent Mg2+ cations and are attractive targets for new antiviral agents. Several structural features of both domains are now available. Drugs targeting the HIV-1 IN are currently approved for anti-HIV therapy, while no drug targeting the HIV-1 RNase H function is yet available. This review describes HIV-1 IN and the RNase H function and structures, compounds targeting their active sites and dual inhibition as a new approach for drug development.