Dual inhibition of HIV-1 replication by integrase-LEDGF allosteric inhibitors is predominant at the post-integration stage

…, B Ledoussal, F Moreau, R Benarous

Index: LABORATOIRE BIODIM; CHASSET, Sophie; CHEVREUIL, Francis; LEDOUSSAL, Benoit; LE STRAT, Frederic; BENAROUS, Richard Patent: WO2012/140243 A1, 2012 ;

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Citation Number: 38

Abstract

Background LEDGF/p75 (LEDGF) is the main cellular cofactor of HIV-1 integrase (IN). It acts as a tethering factor for IN, and targets the integration of HIV in actively transcribed gene regions of chromatin. A recently developed class of IN allosteric inhibitors can inhibit the LEDGF-IN interaction. Results We describe a new series of IN-LEDGF allosteric inhibitors, the most active of which is Mut101. We determined the crystal structure of Mut101 in ...