Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses

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, Xin‐Shan Ye, Lihe Zhang, Demin Zhou · 发表于：Journal of Medicinal Chemistry · 年份：2014 · DOI：10.1021/jm5014067 · 被引用次数：155 · 研究领域：Influenza Virus Research Studies、Immune Response and Inflammation、Glycosylation and Glycoproteins Research

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.