HIV-1 integrase inhibition: binding sites, structure activity relationships and future perspectives.

摘要: The integrase enzyme encoded by the human immunodeficiency virus plays an integral role in viral life cycle, but is as yet unexploited a clinical drug target. Integrase processes DNA cytoplasm, translocates to nucleus, and catalyzes insertion into host genome. A wide variety of chemical structures inhibit vitro, few these apparently promising compounds have demonstrated similar efficacy vivo. Multiple binding targets been identified for different inhibitors. These include prior substrate binding, substrate, preintegration complex consisting oligomeric DNA. Some known inhibitors are effective only presence divalent manganese active site metal ion cofactor, whereas others do not discriminate between magnesium ions. inhibition response ligand at one multiple sites renders derivation simple set structure activity relationships challenging. Progress toward this goal reviewed context experimental theoretical structural information about integrase.