Steindl Theodora M, Crump Carolyn E, Hayden Frederick G, Langer Thierry
Department of Pharmaceutical Chemistry, Institute of Pharmacy, and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria.
J Med Chem. 2005 Oct 6;48(20):6250-60. doi: 10.1021/jm050343d.
The development and application of a sophisticated virtual screening and selection protocol to identify potential, novel inhibitors of the human rhinovirus coat protein employing various computer-assisted strategies are described. A large commercially available database of compounds was screened using a highly selective, structure-based pharmacophore model generated with the program Catalyst. A docking study and a principal component analysis were carried out within the software package Cerius and served to validate and further refine the obtained results. These combined efforts led to the selection of six candidate structures, for which in vitro anti-rhinoviral activity could be shown in a biological assay.
本文描述了一种先进的虚拟筛选和选择方案的开发与应用，该方案采用各种计算机辅助策略来鉴定人鼻病毒衣壳蛋白潜在的新型抑制剂。使用由Catalyst程序生成的高选择性、基于结构的药效团模型，对一个大型的市售化合物数据库进行了筛选。在Cerius软件包中进行了对接研究和主成分分析，以验证并进一步优化所得结果。这些综合努力促成了六种候选结构的选择，在生物学试验中已证明它们具有体外抗鼻病毒活性。
