To accomplish their viral life cycle, lentiviruses such as HIV highjack host
proteins, the so-called cellular co-factors of replication.
Lens Epithelium-derived Growth factor (
LEDGF/p75), a transcriptional co-activator, is a co-factor of
HIV-integrase (IN) and is required for the tethering and correct integration of the viral genome into the host
chromatin. Due to its important role in HIV-replication the
LEDGF/p75-IN interaction is an attractive
antiviral novel target for the treatment of HIV/
AIDS. Intensive
drug discovery efforts over the past years have validated the
LEDGF/p75-IN interaction as a drugable target for
antiviral therapy and have resulted in the design and synthesis of LEDGINs, small molecule inhibitors binding to the dimer interface of
HIV-integrase and inhibiting viral replication with a dual mechanism of action: potent inhibition of the
LEDGF/p75-IN
protein-
protein interaction and allosteric inhibition of the catalytic function. Furthermore they inhibit both early and late steps of the replication cycle which increases their potential for further clinical development. In this review we will highlight the research validating the
LEDGF/p75-IN interaction as a target for
anti-HIV drug discovery and the recent advances in the design and development of LEDGINs.