Inhibitors of human immunodeficiency virus integrase

This chapter focuses on the inhibitors of human immunodeficiency virus integrase. Integration is also essential for the maintenance of persistent infection by keeping the provirus in the host cell genome, ready for production of new infectious viral particles. This chapter outlines recent advances in Integrases (IN) molecular structure and biochemistry that can lead to novel strategies to block retroviral integration, reviews the technical and tactical approaches that have been used and can be developed for inhibitor discovery, and presents an update of the inhibitors identified to date. It also provides complementary information on the in vitro assays used to study the IN inhibitors and extensive lists of known inhibitors of IN. Accruing knowledge of the IN structure, catalytic mechanisms, and interactions with other proteins can be used to design strategies for blocking integration. A large number of inhibitors have been identified that can be used as leads for the development of potent and selective anti-IN drugs with antiviral activity. © 1999 Academic Press Inc.