Structure‐guided Discovery of a Novel Non‐peptide Inhibitor of Dengue Virus NS2B–NS3 Protease. (4th February 2015)

• Record Type: Journal Article
• Authors: Li, Linfeng; Basavannacharya, Chandrakala; Chan, Kitti Wing Ki; Shang, Luqing; Vasudevan, Subhash G.; Yin, Zheng
• Is Part Of: Chemical biology & drug design. Volume 86:Number 3(2015:Sep.)
• Page Start: 255
• Page End: 264
• Publication Date: 2015-02-04
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12500
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12500-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Dengue fever is a fast emerging epidemic‐prone viral disease caused by dengue virus serotypes 1‐4. NS2B–NS3 protease of dengue virus is a validated target to develop antiviral agents. A major limitation in developing dengue virus protease inhibitors has been the lack of or poor cellular activity. In this work, we extracted and refined a pharmacophore model based on X‐ray crystal structure and predicted binding patterns, followed by a three‐dimensional flexible database filtration. These output molecules were screened according to a docking‐based protocol, leading to the discovery of a compound with novel scaffold and good cell‐based bioactivity that has potential to be further optimized. The discovery of this novel scaffold by combination of <italic>in silico</italic> methods suggests that structure‐guided drug discovery can lead to the development of potent dengue virus protease inhibitors.</p> </abstract>