Aureonitol, a Fungi-Derived Tetrahydrofuran, Inhibits Influenza Replication by Targeting Its Surface Glycoprotein Hemagglutinin.

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.

• Authors: Carolina Q Sacramento, Andressa Marttorelli, Natalia Fintelman-Rodrigues, Caroline S de Freitas, Gabrielle R de Melo, Marco E N Rocha, Carlos R Kaiser, Katia F Rodrigues, Gisela L da Costa, Cristiane M Alves, Osvaldo Santos-Filho, Jussara P Barbosa, Thiago Moreno L Souza
• Journal: PloS one (PLoS One) Vol. 10 Issue 10 Pg. e0139236 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26462111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids
• Antiviral Agents
• Furans
• Hemagglutinins
• Membrane Glycoproteins
• aureonitol
• tetrahydrofuran
• Neuraminidase

Topics

• Amino Acids (genetics)
• Animals
• Antiviral Agents (pharmacology)
• Cell Death (drug effects)
• Computer Simulation
• Conserved Sequence
• Dogs
• Dose-Response Relationship, Drug
• Furans (chemistry, pharmacology)
• HEK293 Cells
• Hemagglutination (drug effects)
• Hemagglutinins (chemistry, metabolism)
• Humans
• Influenza A Virus, H3N2 Subtype (drug effects)
• Influenza B virus (drug effects)
• Madin Darby Canine Kidney Cells
• Membrane Glycoproteins (metabolism)
• Neuraminidase (metabolism)
• Time Factors
• Virus Internalization (drug effects)
• Virus Replication (drug effects)