Retroviral Integrase: Difference between revisions

HIV integrase type 1 is a relatively new and novel target for inhibitors.  In 2007, the first HIV-1 integrase inhibitor, Raltegravir, was approved by the FDA for use in HIV-1 as a combination a combination therapy (6).  Strand-transfer inhibitors work by preventing the concerted integration of the viral DNA into the host chromosome.  After viral entry into the host cell, the reverse transcriptase converts the viral ssRNA into dsDNA. At this point, the integrase forms a complex with the viral DNA, creating the pre-integration complex (intasome).  The pre-integration complex is then chaperoned into the nucleus, where two nucleotides are excised from the 3' end.  Next, the DNA is then covalently integrated into the host DNA.  The strand-transfer inhibitors interrupt this process, preventing the integration of the viral DNA into the host chromosome.  Strand-transfer inhibitors work by engaging the metal ion cofactors found in the retroviral integrase active site.  The metal chelating oxygen atoms found in the inhibitors interact directly with the metal cofactors, while the halobenzyl group fits into the pocket created by the displaced 3' viral DNA in the active site.

==Integrase Inhibitors==