Nguyen Hung, Le Ly, Truong Thanh N
Department of Chemistry, University of Utah.
PLoS Curr. 2009 Sep 2;3:RRN1030. doi: 10.1371/currents.RRN1030.
A list of 27 promising antiviral drugs is proposed for use against the H1N1pdm strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of the bird flu H5N1, an effective means to quickly identify top candidates for use against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the NCI diversity set which bind best to H5N1 neuraminidase. These compounds serve as viable candidates for docking against the H1N1pdm neuraminidase, using ensembles extracted from molecular dynamics simulations of the H1N1pdm system. The ranking order of these top candidates was found to be different from the previously published results for H5N1. The results indicated that the Oseltamivir (Tamiflu) and Peramivir drugs have higher ranking than Zanamivir (Relenza). However, six drug candidates were found to bind more effectively to H1N1pdm neuraminidase than Tamiflu. Detailed hydrogen bond network analysis for these six candidates is also provided.
提出了一份包含27种有前景的抗病毒药物的清单，用于对抗甲型H1N1流感病毒（H1N1pdm）毒株。由于甲型H1N1流感病毒神经氨酸酶的结合位点与禽流感H5N1的相似，一种快速确定对抗甲型H1N1流感病毒（H1N1pdm）最佳候选药物的有效方法是使用已知的抗禽流感药物以及美国国立癌症研究所（NCI）多样性集中与H5N1神经氨酸酶结合最佳的27种化合物。这些化合物可作为使用从甲型H1N1流感病毒（H1N1pdm）系统的分子动力学模拟中提取的系综与甲型H1N1流感病毒（H1N1pdm）神经氨酸酶对接的可行候选物。发现这些最佳候选物的排名顺序与先前公布的H5N1结果不同。结果表明，奥司他韦（达菲）和帕拉米韦的排名高于扎那米韦（瑞乐沙）。然而，发现有六种候选药物与甲型H1N1流感病毒（H1N1pdm）神经氨酸酶的结合比达菲更有效。还提供了对这六种候选药物的详细氢键网络分析。
