The H1N1 pandemic in 2009 and the H5N1 outbreak in 2005 have shocked the world as millions of people were infected and hundreds of thousands died due to the infections by the influenza virus. Oseltamivir, the most common drug to block the viral life cycle by inhibiting neuraminidase (NA) enzyme, has been less effective in some resistant cases due to the virus mutation. Presently, the binding of 10 chalcone derivatives towards H5N1 and H1N1 NAs in the non-catalytic and catalytic sites was studied using molecular docking. The in silico study was also conducted for its drug-like likeness such as Lipinski Rule, mutagenicity, toxicity and pharmacokinetic profiles. The result demonstrates that two chalcones (1c and 2b) have the potential for future NA inhibitor development. Compound 1c inhibits H5N1 NA and H1N1 NA with IC50 of 27.63 µM and 28.11 µM, respectively, whereas compound 2b inhibits NAs with IC50 of 87.54 µM and 73.17 µM for H5N1 and H1N1, respectively. The in silico drug-like likeness prediction reveals that 1c is 62% better than 2b (58%) in meeting the criteria. The results suggested that 1c and 2b have potencies to be developed as non-competitive inhibitors of neuraminidase for the future development of anti-influenza drugs.

中文翻译：

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H5N1和H1N1神经氨酸酶作为查尔酮抑制剂靶点的催化和非催化位点研究

2009 年 H1N1 大流行和 2005 年 H5N1 爆发震惊了世界，数百万人被感染，数十万人因流感病毒感染而死亡。奥司他韦是最常见的通过抑制神经氨酸酶 (NA) 来阻断病毒生命周期的药物，但由于病毒突变，在一些耐药病例中效果较差。目前，使用分子对接研究了 10 种查耳酮衍生物在非催化和催化位点与 H5N1 和 H1N1 NAs 的结合。还对其类似药物的相似性进行了计算机研究，例如 Lipinski Rule、致突变性、毒性和药代动力学特征。结果表明，两种查尔酮（1c 和 2b）具有开发未来 NA 抑制剂的潜力。化合物 1c 抑制 H5N1 NA 和 H1N1 NA，IC50 为 27.63 µM 和 28.11 µM，分别，而化合物 2b 抑制 NAs，对 H5N1 和 H1N1 的 IC50 分别为 87.54 µM 和 73.17 µM。计算机模拟药物相似性预测表明，1c 在满足标准方面比 2b (58%) 好 62%。结果表明，1c 和 2b 具有作为神经氨酸酶非竞争性抑制剂的潜力，可用于未来抗流感药物的开发。