the viral DNA to expose an invariant CA dinucleotide at both 3'-ends of the viral DNA. ● the strand transfer reaction, in which the processed 3' ends of the viral DNA are covalently ligated to host chromosomal DNA. Both reactions are catalyzed in the same active site, and involve transesterification without involving a covalent protein-DNA intermediate (in contrast to Ser/Tyr recombinase-catalyzed reactions. In HIV HIV integrase is a 32kDa viral protein consisting of three domains- N-terminus, catalytic core domain, and C-terminus, which each have distinct properties and functions contributing to the efficacy of HIV integrase. The N-terminus is composed of 50 amino acid residues which contain a conserved histidine, histidine, cytosine, cytosine sequence which chelates zinc ions, furthermore enhancing the enzymatic activity of the catalytic core domain. As metal chelation is vital in integrase efficacy, it is a target for the development of retroviral therapies. The catalytic core domain, like the N-terminus, contains highly conserved amino acid residues -Asp64, Asp116, Glu152- as the conserved DDE (Asp-Asp-Glu) motif contributes to the endonuclease and polynucleotide transferase functions of integrase. Mutations in these regions inactivates integrase and prevents genome integration. The C-terminus domain binds to host DNA non-specifically and stabilizes the integration complex. Integration mechanism Following synthesis of HIV's doubled stranded DNA genome, integrase binds to the long tandem repeats flanking the genome on both ends. Using its endonucleolytic activity, integrase cleaves a di or trinucleotide from both 3' ends of the genome in a processing known as 3'-processing. The specificity of cleavage is improved through the use of cofactors such as Mn2+ and Mg2+ which interact with the DDE motif of the catalytic core domain, acting as cofactors to integrase function. The newly generated 3'OH groups disrupt the host DNA's phosphodiester linkages through SN2-type nucleophilic attack. The 3' ends are covalently linked to the target DNA. The 5' over hangs of the viral genome are then cleaved using host repair enzymes, those same enzymes are believed to be responsible for the integration of the 5' end into the host genome forming the provirus. Antiretroviral therapy In November 2005, data from a phase 2 study of an investigational HIV integrase inhibitor, MK-0518, demonstrated that the compound has potent antiviral activity. On October 12, 2007, the Food and Drug Administration (U.S.) approved the integrase inhibitor Raltegravir (MK-0518, brand name Isentress). The second integrase inhibitor, elvitegravir, was approved in the U.S. in August 2012. See