Titolo:  Novel natural non-nucleoside inhibitors of HIV-1 reverse transcriptase identified by shape- and structure-based virtual screening techniques
Data di pubblicazione:  2019
Data di prima pubblicazione on-line:  2018
Autori: 
Autori:  Costa, Giosuè; Rocca, Roberta; Corona, Angela; Grandi, Nicole; Moraca, Federica; Romeo, Isabella; Talarico, Carmine; Giovanna Gagliardi, Maria; Alessandra Ambrosio, Francesca; Ortuso, Francesco; Alcaro, Stefano; Distinto, Simona; Maccioni, Elias; Tramontano, Enzo; Artese, Anna
Numero degli autori:  15
Lingua:  Inglese
Presenza coautori internazionali:  no
Rivista:  EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume:  161
Pagina iniziale:  1
Pagina finale:  10
Numero di pagine:  10
Digital Object Identifier (DOI):  http://dx.doi.org/10.1016/j.ejmech.2018.10.029
Codice identificativo Pubmed:  30342421
Codice identificativo Scopus:  2-s2.0-85054924670
Codice identificativo ISI:  WOS:000451498200001
URL:  https://www.sciencedirect.com/science/article/pii/S0223523418308973?dgcid=coauthor
Abstract:  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 1 (HIV-1) reverse transcriptase (RT) RNA-dependent DNA polymerase activity. Specifically, we screened more than 143000 natural compounds commercially available in the ZINC database against the best five RT 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 RT function and, among them, an indoline pyrrolidine (hit1), an indonyl piperazine (hit2) and an indolyl indolinone (hit3) derivatives were identified as novel non-nucleoside RT inhibitors in the low micromolar range.
Parole chiave:  Reverse transcriptase; NNRTIs; In silico virtual screening; Natural products
Tipologia: 1.1 Articolo in rivista

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