Kuwanon-L as a New Allosteric HIV-1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation
Esposito, F; Tintori, C; Martini, R; Christ, F; Debyser, Z; Ferrarese, R; Cabiddu, G; Corona, A; Ceresola, ER; Calcaterra, A; Iovine, V; Botta, B; Clementi, M; Canducci, F; Botta, M; Tramontano, E; ,
| HERO ID | 7221243 |
|---|---|
| In Press | No |
| Year | 2015 |
| Title | Kuwanon-L as a New Allosteric HIV-1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation |
| Authors | Esposito, F; Tintori, C; Martini, R; Christ, F; Debyser, Z; Ferrarese, R; Cabiddu, G; Corona, A; Ceresola, ER; Calcaterra, A; Iovine, V; Botta, B; Clementi, M; Canducci, F; Botta, M; Tramontano, E; , |
| 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. |
| Doi | 10.1002/cbic.201500385 |
| Pmid | 26360521 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |