BACKGROUND The results of several clinical trials suggest that the integrase inhibitor dolutegravir may be less prone than other drugs to the emergence of HIV drug resistance mutations in treatment-naive patients. We have shown that the R263K mutation commonly emerged during tissue culture selection studies with dolutegravir and conferred low levels of resistance to this drug while simultaneous...

Acquired immunodeficiency syndrome (AIDS) is a formidable pandemic that is still creating havoc world-wide. The curative agent of this disease has been found to be a virus called human immunodeficiency virus of type-1 (HIV-1). In the replicative cycle of HIV-1, the integration of the viral DNA into host chromosomes is an essential step that is catalyzed by the enzyme integrase (IN). Inhibition ...

Acquired immunodeficiency syndrome (AIDS) is a formidable pandemic that is still creating havoc world-wide. The curative agent of this disease has been found to be a virus called human immunodeficiency virus of type-1 (HIV-1). In the replicative cycle of HIV-1, the integration of the viral DNA into host chromosomes is an essential step that is catalyzed by the enzyme integrase (IN). Inhibition ...

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...

Integration is a crucial step in the life cycle of human immunodeficiency virus type 1 (HIV-1); therefore, inhibitors of HIV-1 integrase are candidates for antiretroviral therapy. Two 7-hydroxytropolone derivatives ( -hydroxytropolones) were found to inhibit HIV-1 integrase. A structure-activity relationship investigation with several tropolone derivatives from The National Cancer Institute com...

S/GSK1349572 is a next-generation HIV integrase (IN) inhibitor designed to deliver potent antiviral activity with a low-milligram once-daily dose requiring no pharmacokinetic (PK) booster. In addition, S/GSK1349572 demonstrates activity against clinically relevant IN mutant viruses and has potential for a high genetic barrier to resistance. S/GSK1349572 is a two-metal-binding HIV integrase stra...

Temperate Myxococcus xanthus phage Mx8 integrates into the attB locus of the M. xanthus genome. The phage attachment site, attP, is required in cis for integration and lies within the int (integrase) coding sequence. Site-specific integration of Mx8 alters the 3' end of int to generate the modified intX gene, which encodes a less active form of integrase with a different C terminus. The phage-e...

Phage integrase-based circuits are an alternative approach to relying on transcriptional and translational repression for biomolecular circuits. Previous research has shown that circuits based on integrases can perform a variety of functions, including counters, Boolean logic operators, memory modules and temporal event detectors. It is therefore essential to develop a principled theoretical an...

Integrase is the only viral protein necessary for integration of retroviral DNA into chromosomal DNA of the host cell. Biochemical analysis of human immunodeficiency virus type 1 (HIV-1) integrase with purified protein and synthetic DNA substrates has revealed extensive information regarding the mechanism of action of the enzyme, as well as identification of critical residues and functional dom...

Internet Electronic Conference of Molecular Design 2003, November 23 – December 6 Abstract Motivation. A continuous demand exists for novel bioactive molecules. When a lead structure has been discovered and looks promising for further development, series of analogues will be made. Normally, the synthesis of many compounds is required to improve on the activity, or to keep good activity while op...