High-throughput docking for the identification of new influenza A virus polymerase inhibitors targeting the PA-PB1 protein-protein interaction

被引：31
作者：
Tintori, Cristina [1 ]
Laurenzana, Ilaria [2 ]
Fallacara, Anna Lucia [1 ,3 ]
Kessler, Ulrich [4 ]
Pilger, Beatrice [4 ]
Stergiou, Lilli [4 ]
Botta, Maurizio [1 ,5 ]
机构：
[1] Univ Siena, Dipartimento Biotecnol Chim & Farm, I-53100 Siena, Italy
[2] IRCCS, Ctr Riferimento Oncol Basilicata, Lab Preclin & Translat Res, I-85028 Potenza, Italy
[3] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farm, I-00185 Rome, Italy
[4] Swiss Fed Inst Technol, Inst Pharmaceut Sci, PiKe Pharma GmbH, CH-8093 Zurich, Switzerland
[5] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 01期
关键词：
Antiviral agents; Influenza virus; Viral RNA polymerase; Virtual screening; High-throughput docking; PA-PB1; interaction; VIRAL POLYMERASE; AVIAN INFLUENZA; H5N1; VIRUS; B VIRUSES; DISCOVERY;
D O I：
10.1016/j.bmcl.2013.11.019
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A high-throughput molecular docking approach was successfully applied for the selection of potential inhibitors of the Influenza RNA-polymerase which act by targeting the PA-PB1 protein-protein interaction. Commercially available compounds were purchased and biologically evaluated in vitro using an ELISA-based assay. As a result, some compounds possessing a 3-cyano-4,6-diphenyl-pyridine nucleus emerged as effective inhibitors with the best ones showing IC50 values in the micromolar range. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码：280 / 282
页数：3
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