Title: New scaffolds of natural origin as Integrase-LEDGF/p75 interaction inhibitors: Virtual screening and activity assays
Authors: De Luca, Laura * ×
Morreale, Francesca *
Christ, Frauke
Debyser, Zeger
Ferro, Stefania
Gitto, Rosaria #
Issue Date: Aug-2013
Series Title: European Journal of Medicinal Chemistry vol:68 pages:405-411
Article number: S0223-5234(13)00473-X
Abstract: The disruption of crucial interactions between HIV-1 Integrase and cellular cofactor LEDGF/p75 represents an emerging approach for the design and development of new antiretroviral agents. In this study we report the successful application of a structure-based virtual screening strategy for the discovery of natural hit structures able to inhibit Integrase-LEDGF/p75 interaction. The application of sequential filters (drug-likeness, 3D-pharmacophore mapping, docking, molecular dynamics simulations) yielded a hit list of compounds, out of which 9 were tested in the in vitro AlphaScreen assays and 8 exhibited a detectable inhibition of the interaction between the two proteins. The best inhibitors belong to different chemical classes and could be represent a good starting point for further optimization and structure-activity relationship studies.
ISSN: 0223-5234
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
* (joint) first author
× corresponding author
# (joint) last author

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