2. Academic Validation
  3. Neoechinulin B and its analogues as potential entry inhibitors of influenza viruses, targeting viral hemagglutinin

Neoechinulin B and its analogues as potential entry inhibitors of influenza viruses, targeting viral hemagglutinin

  • Eur J Med Chem. 2015 Mar 26:93:182-95. doi: 10.1016/j.ejmech.2015.02.006.
Xueqing Chen 1,  Longlong Si 1,  Dong Liu 1,  Peter Proksch 2,  Lihe Zhang 1,  Demin Zhou 3,  Wenhan Lin 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
  • 2 Institute für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, Geb.26.23, 40225 Düsseldorf, Germany.
  • 3 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address: deminzhou@bjmu.edu.cn.
  • 4 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. Electronic address: whlin@bjmu.edu.cn.
PMID: 25681711 DOI: 10.1016/j.ejmech.2015.02.006
Abstract

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.

Keywords

Eurotium rubrum; Hemagglutinin; Influenza virus entry inhibitor; Neoechinulin B; Prenylated indole diketopiperazines.

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