Rational design of LEDGINs as first allosteric integrase inhibitors for the treatment of HIV infection

The interaction between lens epithelium-derived growth factor (LEDGF/p75) and HIV-1 integrase (IN) is an attractive target for antiviral development because its inhibition blocks HIV replication. Developing novel small molecules that disrupt the LEDGF/p75–IN interaction constitutes a promising new therapeutic strategy for the treatment of HIV. Here we will highlight recent advances in the design and development of small-molecule inhibitors binding to the LEDGF/p75 binding pocket of IN, referred to as LEDGINs.