HIV-1 integrase as a target for antiviral drugs

Retrovirus integration requires at least two viral components, one of the three retroviral enzymes, integrase, and cis-acting sequences at the ends of the retroviral DNA termini U3 and U5 ends of the long terminal repeats. Because the virus cannot replicate without integration into a host chromosome, integrase is a logical therapeutic target. Therapeutic inhibitors already exist for reverse transcriptase and protease, and attacking the virus on these sites together has already proven effective for combination therapy. Thus, the discovery of integrase inhibitors should provide an additional benefit. Screening and pharmacology of anti-integrase drugs is facilitated by the cloning and expression of recombinant retroviral integrases and their use in a series of in vitro assays that mimic integration in vivo. This review first describes the integration reactions in the retrovirus life cycle and the integrase protein. Then we provide a comprehensive review of the inhibitors identified to date.