Agamennone Mariangela, Pietrantoni Agostina, Superti Fabiana
Department of Pharmacy, University "G. d'Annunzio", Via dei Vestini 31, 66100 Chieti, Italy.
Department of Technology and Health, National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.
Virology. 2016 Jan 15;488:249-58. doi: 10.1016/j.virol.2015.11.024. Epub 2015 Dec 3.
Influenza virus represents a serious threat to public health. The lack of effective drugs against flu prompted researchers to identify more promising viral target. In this respect hemagglutinin (HA) can represent an interesting option because of its pivotal role in the infection process. With this aim we collected a small library of commercially available compounds starting from a large database and performing a diversity-based selection to reduce the number of screened compounds avoiding structural redundancy of the library. Selected compounds were tested for their hemagglutination-inhibiting (HI) ability against two different A/H1N1 viral strains (one of which is oseltamivir sensitive), and 17 of them showed the ability to interact with HA. Five drug-like molecules, in particular, were able to impair hemagglutination of both A/H1N1 viral strains under study and to inhibit cytopathic effect and hemolysis at sub-micromolar level.
流感病毒对公众健康构成严重威胁。缺乏有效的抗流感药物促使研究人员寻找更有前景的病毒靶点。在这方面，血凝素（HA）因其在感染过程中的关键作用而可能是一个有趣的选择。出于这个目的，我们从一个大型数据库开始收集了一个小型的市售化合物库，并进行基于多样性的筛选以减少筛选化合物的数量，避免库中的结构冗余。对所选化合物针对两种不同的A/H1N1病毒株（其中一种对奥司他韦敏感）的血凝抑制（HI）能力进行了测试，其中17种显示出与HA相互作用的能力。特别是有五种类药物分子能够抑制所研究的两种A/H1N1病毒株的血凝，并在亚微摩尔水平抑制细胞病变效应和溶血。
