The catalytic site of the HIV integrase is contained within an RNase H-like fold, and numerous drugs have been developed that bind to this site and inhibit its activity. Herpes simplex virus (HSV) encodes two proteins with potential RNase H-like folds, the infected cell protein 8 (ICP8) DNA-binding protein, which is necessary for viral DNA replication and exhibits recombinase activity in vitro,...

A new series of AT-specific minor groove DNA ligands (DB3P(n); n = 1,2,3,4) was synthesized and their spectral, biological virological properties were investigated. With a methylene spacers different lengths blocks three AT pairs located at distances from each other could be recognized. The compounds suppressed the activity HIV-1 integrase submicromolar concentrations (0.25–0.50 µМ). Also, DB3P...

Signature HIV-1 integrase mutations associated with clinical raltegravir resistance involve 1 of 3 primary genetic pathways, Y143C/R, Q148H/K/R and N155H, the latter 2 of which confer cross-resistance to elvitegravir. In accord with clinical findings, in vitro drug resistance profiling studies with wild-type and site-directed integrase mutant viruses have shown significant fold increases in ral...

HIV integrase, encoded at the 3'-end of the HIV pol gene, is essential for HIV replication. This enzyme catalyzes the incorporation of HIV DNA into human DNA, which represents the point of "no-return" in HIV infection. Integrase is a significant target in anti-HIV drug discovery. This review article focuses largely on the design of integrase inhibitors that are β-diketo acids constructed on pyr...

Due to the mutation of HIV enzymes and their resistance against current drugs, drug companies are exploring ways to develop stronger mutant resistant drugs. Dimeric aryl diketo acids have proven to be effective inhibitors to the HIV strand transfer mechanism of HIV-integrase. In order to create the best drug to fight HIV-integrase, it is important to know which features of the diketo acids have...

We present the first receptor-based pharmacophore model for HIV-1 integrase. The development of "dynamic" pharmacophore models is a new method that accounts for the inherent flexibility of the active site and aims to reduce the entropic penalties associated with binding a ligand. Furthermore, this new drug discovery method overcomes the limitation of an incomplete crystal structure of the targe...