Title: Discovery of novel influenza inhibitors targeting the interaction of dsRNA with the NS1 protein by structure-based virtual screening

Authors: Haixin Ai, Fangliang Zheng, Chunyu Zhu, Tingting Sun, Li Zhang, Xue Liu, Xuejiao Li, Guangyu Zhu, Hongsheng Liu

Addresses: School of Life Science, Liaoning University, Shenyang 110036, China; Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning, Shenyang 110036, China. ' School of Life Science, Liaoning University, Shenyang 110036, China; Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning, Shenyang 110036, China. ' School of Life Science, Liaoning University, Shenyang 110036, China. ' School of Life Science, Liaoning University, Shenyang 110036, China. ' School of Life Science, Liaoning University, Shenyang 110036, China. ' School of Life Science, Liaoning University, Shenyang 110036, China. ' School of Life Science, Liaoning University, Shenyang 110036, China. ' School of Life Science, Liaoning University, Shenyang 110036, China. ' School of Life Science, Liaoning University, Shenyang 110036, China; Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning, Shenyang 110036, China

Abstract: Influenza A Non-structural protein 1 (NS1A) RNA-Binding Domain (RBD) bound to a double-stranded RNA (dsRNA), which can inhibit the activation of antiviral pathway. The chemical compound binding sites at this pocket have abilities to block NS1 protein to inhibit dsRNA-dependent activation transfected beta interferon promoter construct. The molecular docking program AUTODOCK was used for virtual screening of about 200,000 compounds. Two more typical compounds were selected as the starting point for predicting binding modes. Further analysis shows that these compounds candidates of antiinfluenza drug, which provide an important reference for discovering new influenza virus drugs.

Keywords: influenza inhibitors; flu inhibitors; NS1A-RBD; virtual screening; autodock dsRNA; compound database; NAMD; molecular docking; bioinformatics; binding modes; drug discovery.

DOI: 10.1504/IJBRA.2010.037985

International Journal of Bioinformatics Research and Applications, 2010 Vol.6 No.5, pp.449 - 460

Published online: 07 Jan 2011 *

Full-text access for editors Full-text access for subscribers Purchase this article Comment on this article