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

• Rubrumlines A–O were isolated as new alkaloids from fungus Eurotium rubrum.
• Neoechinulin B exerted potent inhibition against H1N1 virus infected in MDCK cells.
• Neoechinulin B inhibited a panel of drug resistant clinical isolates.
• Neoechinulin B targeted at hemagglutinin to disrupt the interaction of HA with the sialic acid receptor.

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.

Neoechinulin B exerted potent inhibition against H1N1 virus infected in MDCK cells and the drug-resistant clinical isolates by targeting hemagglutinin to disrupt the interaction of HA with the sialic acid receptor.Figure optionsDownload as PowerPoint slide