Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses

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• 作者：Maorong Yu ; Longlong Si ; Yufei Wang ; Yiming Wu ; Fei Yu ; Pingxuan Jiao ; Yongying Shi ; Han Wang ; Sulong Xiao ; Ge Fu ; Ke Tian ; Yitao Wang ; Zhihong Guo ; Xinshan Ye ; Lihe Zhang ; Demin Zhou
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：December 11, 2014
• 年：2014
• 卷：57
• 期：23
• 页码：10058-10071
• 全文大小：779K
• ISSN：1520-4804

文摘

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鈥揳ctivity 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.