Open AccessAureonitol, a Fungi-Derived Tetrahydrofuran, Inhibits Influenza Replication by Targeting Its Surface Glycoprotein Hemagglutinin
Author(s) -
Carolina Q. Sacramento,
Andressa Marttorelli,
Natália Fintelman-Rodrigues,
Caroline de Freitas,
Gabrielle R. de Melo,
Marco E. N. Rocha,
Carlos R. Kaiser,
Kenneth Francis Rodrigues,
Gisela Lara da Costa,
Cristiane M. Alves,
Osvaldo A. SantosFilho,
Julianna Freires Barbosa,
Thiago Moreno L. Souza
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0139236
Subject(s) - neuraminidase , hemagglutinin (influenza) , virology , influenza a virus , sialic acid , microbiology and biotechnology , virus , biology , h5n1 genetic structure , antiviral drug , chemistry , medicine , biochemistry , infectious disease (medical specialty) , disease , covid-19 , pathology
The influenza virus causes acute respiratory infections, leading to high morbidity and mortality in groups of patients at higher risk. Antiviral drugs represent the first line of defense against influenza, both for seasonal infections and pandemic outbreaks. Two main classes of drugs against influenza are in clinical use: M2-channel blockers and neuraminidase inhibitors. Nevertheless, because influenza strains that are resistant to these antivirals have been described, the search for novel compounds with different mechanisms of action is necessary. Here, we investigated the anti-influenza activity of a fungi-derived natural product, aureonitol. This compound inhibited influenza A and B virus replication. This compound was more effective against influenza A(H3N2), with an EC 50 of 100 nM. Aureonitol cytoxicity was also very low, with a CC 50 value of 1426 μM. Aureonitol inhibited influenza hemagglutination and, consequently, significantly impaired virus adsorption. Molecular modeling studies revealed that aureonitol docked in the sialic acid binding site of hemagglutinin, forming hydrogen bonds with highly conserved residues. Altogether, our results indicate that the chemical structure of aureonitol is promising for future anti-influenza drug design.