Inhibitors of the Interactions between HIV-1 IN and the Cofactor LEDGF/p75

he replication cycle of human immunodeficiency virus type1 (HIV-1) is a complex multistep process that depends on both viral and host cell factors. The nuclear protein lens epithelium-derived growth factor (LEDGF/p75) is a multidomain protein, present in host cells, which plays an important role in the integration process. LEDGF/p75 not only binds HIV-1 integrase (IN) at its IN binding domain (IBD) but also contains several motifs that function in DNA and chromatin binding. The demonstrated importance of the association between IN and LEDGF/p75 in HIV-1 integration suggests the possibility that this protein-protein interaction (PPI) could be exploited as an antiviral target. We describe herein the progress to date in developing inhibitors of this promising target. Getting in between: Protein-protein interactions are increasingly important targets for drug development against a number of diseases, including HIV. The interface between HIV-1 integrase (IN) and the cofactor LEDGF/p75 is a very promising target in this regard, and significant advances toward new inhibitors have been made in recent years. Herein we discuss the progress in the development of peptides and small-molecule inhibitors that specifically target the interaction between HIV-1 IN and LEDGF/p75.