Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses
Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses
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发现五环三萜类化合物作为流感病毒的潜在进入抑制剂
DOI：
10.1021/jm5014067
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发表时间：
2014
影响因子：
7.3
通讯作者：
Zhou Demin
中科院分区：
文献类型：
--
作者：
Yu Maorong;Si Longlong;Wang Yufei;Wu Yiming;Yu Fei;Jiao Pingxuan;Shi Yongying;Wang Han;Xiao Sulong;Fu Ge;Tian Ke;Wang Yitao;Guo Zhihong;Ye Xinshan;Zhang Lihe;Zhou Demin
进入抑制剂在目前开发新一代抗流感病毒药物的努力中特别重要。在这里，我们报告了某些五环三萜类化合物，它们具有保守的结构特征，并且具有与奥司他韦相当甚至更高的体外抗流感病毒活性。机制研究表明，这些铅三萜类化合物紧密结合病毒包膜血凝素（HA），破坏HA与唾液酸受体的相互作用，从而破坏病毒对宿主细胞的附着。对接研究表明，HA内唾液酸受体的结合口袋可能作为靶向结构域，这得到了结构-活性数据、唾液酸竞争研究、广泛的抗流感谱以及较少的耐药性诱导的支持。我们的研究可能会建立的重要性，三萜类化合物的发展，进入抑制剂的流感病毒。
Entry inhibitors are of particular importance in current efforts to develop a new generation of anti-influenza virus drugs. Here we report certain pentacyclic triterpenes exhibiting conserved structure features and with in vitro anti-influenza virus activity comparable to and even higher than that of oseltamivir. Mechanistic studies indicated that these lead triterpenoids bind tightly to the viral envelope hemagglutinin (HA), disrupting the interaction of HA with the sialic acid receptor and thus the attachment of viruses to host cells. Docking studies suggest that the binding pocket within HA for sialic acid receptor potentially acts as a targeting domain, and this is supported by structure–activity data, sialic acid competition studies, and broad anti-influenza spectrum as well as less induction of drug resistance. Our study might establish the importance of triterpenoids for development of entry inhibitors of influenza viruses.