Inhibitors of the interactions between HIV-1 IN and the cofactor LEDGF/p75.
2011
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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