A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer inhibitors (INSTIs) were evaluated in vitro in cell-free enzyme activity assays...

Retroviral integrases are essential for viral replication and represent an attractive chemotherapeutic target. In the current study, we demonstrated the activity of micromolar concentrations of dinucleotides against human immunodeficiency virus type 1 (HIV-1), HIV type 2 (HIV-2), simian immunodeficiency virus, and feline immunodeficiency virus integrases. The structure-activity relationship ind...

Some new diazo incorporated coumarin compounds were designed and synthesized to evaluate their anti-HIV activity. Overall, compounds were active against HIV at 100 μM. Additionally, no cytotoxic effect was observed at this concentration. The compound with 4-chlorobenzyl group indicated the best anti-HIV activity (52%). Docking studies using the later crystallographic data available for PFV inte...

R etroviruses covalently insert their genome into the DNA of the host cell and subsequently coopt cellular machinery for DNA replication, transcription, and protein expression (1). These viruses also exploit cellular proteins to assist in this stable insertion of their genetic material into the host genome, a process called integration. In a recent issue of PNAS, Cherepanov et al. (2) reported ...

Understanding the HIV integrase protein and mechanisms of resistance to HIV integrase inhibitors is complicated by the lack of a full length HIV integrase crystal structure. Moreover, a lentiviral integrase structure with co-crystallised DNA has not been described. For these reasons, we have developed a structural method that utilizes free software to create quaternary HIV integrase homology mo...

hiv-1 integrase (in) enzyme, one of the three main enzymes of hiv-1, catalyzed the insertion of the viral dna into the genome of host cells. because of the lack of its homologue in human cells and its essential role in hiv-1 replication, in inhibition represents an attractive therapeutic target for hiv-1 treatment. since identification of in as a promising therapeutic target, a major progress h...

C an retroviral integration be targeted to preselected locations in the human genome? If so, targeting might improve the safety of retroviral vectors for use in gene therapy. Directing integration of vectors to benign locations in the human genome, for example, might reduce the risk of transformation by insertional activation of oncogenes. This issue has become a lot less theoretical with the r...

The development of multiple agents with potent antiretroviral activity against HIV has ushered in a new age of optimism in the management of patients infected with the virus. However, the viruses' dynamic ability to develop resistance against these agents necessitates the investigation of novel targets for viral suppression. Raltegravir represents a first-in-class agent targeting the HIV integr...

The oligomeric state of active human immunodeficiency virus type 1 (HIV-1) integrase (IN) has not been clearly elucidated. We analyzed the activity of the different purified oligomeric forms of recombinant IN obtained after stabilization by platinum crosslinking. The crosslinked tetramer isolated by gel chromatography was able to catalyze the full-site integration of the two viral LTR ends into...

The karyophilic properties of the HIV-1 nucleoprotein complex facilitate infection of nondividing cells such as macrophages and quiescent T lymphocytes, and allow the in vivo delivery of transgenes by HIV-derived retroviral vectors into terminally differentiated cells such as neurons. Although the viral matrix (MA) and Vpr proteins have previously been shown to play important roles in this proc...