Fueling HIV-1 integrase drug design with structural insights

Integrase (IN) is the last of the three Human Immunodeficiency Virus-1 (HIV-1) enzymes to be targeted by antiretroviral therapy. At present, a single integration inhibitor (raltegravir) has been approved for clinical use. Rapid emergence of drug resistance warrants development of novel inhibitors. Fortunately, the past few years have brought forth a tremendous increase in the understanding of the molecular and structural biology of integration. We discuss recent discoveries as well as novel opportunities for structure-based design in the quest for novel IN inhibitors.