Small molecules targeting protein-protein interactions: A promising anti-HIV strategy
Chimirri, Alba De Luca, Laura Ferro, Stefania Gitto, Rosaria Monforte, Anna Maria Agnello, Stefano Barreca, Maria Letizia Christ, Frauke Debyser, Zeger #
Antiviral Research vol:86 issue:1 pages:A32-A32
International Conference on Antiviral Research edition:23 location:San Francisco, USA date:25-28 April 2010
The development of multidrug-resistant viruses compromises the efficacy of anti-human immunodeficiency virus (HIV) therapy and limits treatment options. Therefore, new targets with a different mechanism of action with respect to anti-AIDS drugs so far in therapy need to be identified. In recent years, many examples of protein–protein interactions in the HIV life cycle and related inhibitors is growing rapidly (Busschots et al., 2009). Thus, protein–protein interactions (PPIs) provide an important new approach for the drug design against HIV infection. In our previous paper, a structure-based 3D pharmacophore model for potential inhibitors of the interaction between HIV-1-IN and its cellular cofactor LEDGF/p75 was developed and used for virtual screening of chemical databases, leading to the identification of interesting hits for further optimization (De Luca et al., 2009). Consequently, the rational design, synthesis and biological tests of some derivatives have been carried out. Our studies resulted in the discovery of compounds able to interfere with the IN-LEDGF/p75 interaction at micromolar concentration. Docking simulations were also performed with the aim to investigate the possible binding mode of our new compounds. Acknowledgement: Research supported by THINC project(HEALTH-F3-2008-201032).