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.
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Authors | Xueqing Chen, Longlong Si, Dong Liu, Peter Proksch, Lihe Zhang, Demin Zhou, Wenhan Lin |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 93
Pg. 182-95
(Mar 26 2015)
ISSN: 1768-3254 [Electronic] France |
PMID | 25681711
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Alkaloids
- Antiviral Agents
- H1N1 virus hemagglutinin
- Hemagglutinin Glycoproteins, Influenza Virus
- Piperazines
- neoechinulin
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Topics |
- Alkaloids
(chemical synthesis, chemistry, isolation & purification, pharmacology)
- Animals
- Antiviral Agents
(chemical synthesis, chemistry, isolation & purification, pharmacology)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Cytopathogenic Effect, Viral
- Dogs
- Dose-Response Relationship, Drug
- Drug Resistance, Viral
(drug effects)
- Eurotium
(chemistry)
- HEK293 Cells
- Hemagglutinin Glycoproteins, Influenza Virus
(metabolism)
- Humans
- Influenza A Virus, H1N1 Subtype
(drug effects, growth & development, metabolism)
- Madin Darby Canine Kidney Cells
- Molecular Structure
- Piperazines
(chemical synthesis, chemistry, isolation & purification, pharmacology)
- Structure-Activity Relationship
- Viral Plaque Assay
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