Development of Anti-Influenza Drugs of Next Generation Which Conquest Vral Mutation and Inhibit Both Steps of Viral Entry and Release

1.发现了一种能阻断流感病毒进入宿主细胞和从宿主细胞释放的新唾液酸类化合物：Neu5Ac3-αF-二硬脂酰磷脂酰乙醇胺，其C-3位被轴向氟原子修饰，能抑制流感病毒唾液酸酶的催化水解和血凝素的结合活性。对唾液酸酶的抑制活性与所分离的病毒无关。研究表明，该化合物是一类新型的双功能药物，可用于未来的流感化疗。利用内切糖苷酶(Endo-Gidesidase，Endo-M)一锅转糖法制备了双唾液酸络合型低聚糖的三联吡啶Ru-配合物，它们与甲型流感病毒有很好的亲和力(IC_(50)=8.4μM)，其发光强度受到病毒结合的强烈抑制。这一结果表明，所得到的Ru-cpmplex适用于一种新的流感-感觉系统。在鸡胚蛋中发现并分离出一种新的唾液酸鞘糖脂(神经节苷脂)，它能结合并强烈抑制所有受试的人和动物流感病毒的感染。通过质谱分析确定了部分化学结构。提示该神经节苷脂可能是自然界中流感病毒的内源性受体分子之一。该衍生物可能适用于未来开发一种较强的抗流感药物。一些天然和人工合成的化合物，如携带唾液酸链的人工粘蛋白，或与唾液乳糖连接的环肽，被发现能抑制流感的复制。

1. The discovery of a new sialocompound which blocks both process of the entry into and release from the host cells of influenza viruses: Neu5Ac3 α F-distearoylphoshatidy lethanolamine in which the C-3 position was modified with an axial fluorine atom, was found to inhibit the catalytic hydrolysis of influenza virus sialidase and the binding activity of hemagglutinin. The inhibitory activities to sialidases were independent of virus isolated examined. The study suggested that the compound is a bew class of bifunctional drug candidates for the future chemotherapy of influenza.2. Tris-bipyridine ruthenium-complex carrying a disialo complex-type oligosaccharide were prepared via a one-pot transglycosylation using endo-glycosidase (Endo M); they bind to type-A influenza viruses with excellent affinity (IC50 = 8.4 μM), and their luminescence intensity is strongly depressed by virus-binding. This result indicate that the resulting ruthenium-cpmplex is applicable to a new influenza-sensory system.3. A new sialo-glycosphingolipid (Ganglioside) which binds and strongly inhibits the infection of every human and animal influenza viruses tested was found in and isolated from embryonate chicken eggs. A part of the chemical structure was determined by the analyses of Mass spectrometry. It is suggested that this ganglioside may be one of the real endogenous receptor molecule for influenza viruses in nature. This derivative may applicable to develop a strong anti-influenza drugs in future.4. Several native and synthesized compounds such as artificial mucin carrying sialyllacto-series sugar chain, or cyclic peptide to which sialyllactose connected were found to inhibit the influenza replication.