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

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Abstract
The replication cycle of human immunodeficiency virus type 1 (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.

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