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AUREONITOL, A FUNGI-DERIVED TETRAHYDROFURAN, INHIBITS INFLUENZA REPLICATION BY TARGETING ITS SURFACE GLYCOPROTEIN HEMAGGLUTININ
Vírus da Influenza A
Vírus da Influenza B
Aureonitol
Fungi-Derived Tetrahydrofuran
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Affilliation
Abstract
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 EC50 of 100 nM. Aureonitol cytoxicity
was also very low, with a CC50 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.
Keywords
Glycoprotein HemagglutininVírus da Influenza A
Vírus da Influenza B
Aureonitol
Fungi-Derived Tetrahydrofuran
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