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Neoechinulin B and its analogues as potential entry inhibitors of influenza viruses, targeting viral hemagglutinin
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2015-02-07 , DOI: 10.1016/j.ejmech.2015.02.006
Xueqing Chen , Longlong Si , Dong Liu , Peter Proksch , Lihe Zhang , Demin Zhou , Wenhan Lin

A class of prenylated indole diketopiperazine alkaloids including 15 new compounds namely rubrumlines A-O obtained from marine-derived fungus Eurotium rubrum, were tested against influenza A/WSN/33 virus. Neoechinulin B (18) exerted potent inhibition against H1N1 virus infected in MDCK cells, and is able to inhibit a panel of influenza virus strains including amantadine- and oseltamivir-resistant clinical isolates. Mechanism of action studies indicated that neoechinulin B binds to influenza envelope hemagglutinin, disrupting its interaction with the sialic acid receptor and the attachment of viruses to host cells. In addition, neoechinulin B was still efficient in inhibiting influenza A/WSN/33 virus propagation even after a fifth passage. The high potency and broad-spectrum activities against influenza viruses with less drug resistance make neoechinulin B as a new lead for the development of potential inhibitor of influenza viruses.



中文翻译:

新棘球蛋白B及其类似物作为靶向病毒血凝素的流感病毒的潜在进入抑制剂

一类的异戊烯化的吲哚二酮哌嗪类生物碱包括15个新的化合物,即rubrumlines AO从海洋来源的真菌得到的散囊菌癣菌,分别针对流感A测试/ WSN / 33病毒。新蛋白B(18)对被MDCK细胞感染的H1N1病毒具有有效的抑制作用,并且能够抑制一系列包括金刚烷胺和奥司他韦耐药的临床分离株在内的流感病毒株。作用机理研究表明,新棘球蛋白B与流感包膜血凝素结合,破坏了它与唾液酸受体的相互作用以及病毒与宿主细胞的附着。此外,即使在第五次传代后,新棘霉素B仍能有效抑制A / WSN / 33流感病毒的传播。对耐药性较小的流感病毒的高效力和广谱活性使新棘球蛋白B成为开发潜在的流感病毒抑制剂的新途径。

更新日期:2015-02-07
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