Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593820 | Bioorganic & Medicinal Chemistry Letters | 2012 | 5 Pages |
Abstract
Efficacy of currently approved anti-HIV drugs is hampered by mutations of the viral enzymes, leading invariably to drug resistance and chemotherapy failure. Recent data suggest that cellular co-factors also represent useful targets for anti-HIV therapy. Here we describe the identification of the first small molecules specifically designed to inhibit the HIV-1 replication by targeting the RNA binding site of the human DEAD-Box RNA helicase DDX3. Optimization of a easily synthetically accessible hit (1) identified by application of a high-throughput docking approach afforded the promising compounds 6 and 8 which proved to inhibit both the helicase and ATPase activity of DDX3 and to reduce the viral load of peripheral blood mononuclear cells (PBMC) infected with HIV-1.
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Authors
Marco Radi, Federico Falchi, Anna Garbelli, Alberta Samuele, Vincenzo Bernardo, Stefania Paolucci, Fausto Baldanti, Silvia Schenone, Fabrizio Manetti, Giovanni Maga, Maurizio Botta,