Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/6516
Title: Kuwanon-L as a New Allosteric HIV-1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation
Authors: Esposito, Francesca
TINTORI, CRISTINA
MARTINI, RICCARDO
Christ, Frauke
Debyser, Zeger
Ferrarese, Roberto
Cabiddu, Gianluigi
Corona, Angela
Ceresola, Elisa Rita
Calcaterra, Andrea
Iovine, Valentina
Botta, Bruno
Clementi, Massimo
Canducci, Filippo
Botta, Maurizio 
Tramontano, Enzo
Keywords: HIV-1 integrase; allosterism; inhibitors; integrase multimerization; kuwanon-L; protein-protein interactions
Issue Date: 2015
Project: None 
Journal: CHEMBIOCHEM
Abstract: 
HIV-1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand-transfer drug-resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking-based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon-L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon-L is able to inhibit the HIV-1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon-L also inhibited HIV-1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon-L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents.
Description: 
204467
URI: http://hdl.handle.net/20.500.12779/6516
ISSN: 1439-4227
DOI: 10.1002/cbic.201500385
Appears in Collections:Publications

Show full item record

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.