期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 161, 期 -, 页码 1-10出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.10.029
关键词
Reverse transcriptase; NNRTIs; In silico virtual screening; Natural products
资金
- Italian Ministry of Education [FIRB-IDEAS RBID082ATK]
In this work we report a parallel application of both docking- and shape-based virtual screening (VS) methods, followed by Molecular Dynamics simulations (MDs), for discovering new compounds able to inhibit the human immunodeficiency virus type I (HIV-1) reverse transcriptase (RI) RNA-dependent DNA polymerase activity. Specifically, we screened more than 143000 natural compounds commercially available in the ZINC database against the best five RI crystallographic models, taking into account the five approved NNRTIs as query compounds. As a result, 20 hit molecules were selected and tested on biochemical assays for the inhibition of the RNA dependent DNA polymerase RI function and, among them, an indoline pyrrolidine (hit 1), an indonyl piperazine (hit 2) and an indolyl indolinone (hit 3) derivatives were identified as novel non-nucleoside RI inhibitors in the low micromolar range. (C) 2018 Elsevier Masson SAS. All rights reserved.
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