Glycyrrhizin inhibits influenza A virus uptake into the cell

• Published in: Antiviral research Vol. 83; no. 2; pp. 171 - 178
• Main Authors: Wolkerstorfer, Andrea, Kurz, Harald, Bachhofner, Nicole, Szolar, Oliver H.J.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.08.2009; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral agents; Antiviral Agents - pharmacology; Biological and medical sciences; Cell Line; Epithelial Cells - virology; Glycyrrhiza - chemistry; Glycyrrhiza glabra; Glycyrrhizic Acid - pharmacology; Glycyrrhizin; Human viral diseases; Humans; Infectious diseases; Influenza A virus; Influenza A virus - drug effects; Influenza A virus - physiology; Medical sciences; Pharmacology. Drug treatments; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Virus Internalization - drug effects; Virus uptake; Glycyrrhizin; Virus uptake; Influenza A virus; GL; Antiviral activity; IAV; Antiinflammatory agent; Orthomyxoviridae; Exploration; Licorice; In vitro; Uptake; Infection; Virus; Influenzavirus A; Glycyrrhizic acid; Viral disease; Antiviral; Influenza A; Cell
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2009.04.012

We investigated the mechanism by which glycyrrhizin (GL), the main active component of licorice roots, protects cells from infection with influenza A virus (IAV). We found that GL treatment leads to a clear reduction in the number of IAV-infected human lung cells as well as a reduction in the CCID50 titer by 90%. The antiviral effect, however, was limited to one or two virus replication cycles. Analysis of different GL treatment protocols suggested that the antiviral effect of GL was limited to an early step in the virus replication cycle. A direct inhibitory action of GL on IAV particles could be excluded and GL did not interact with virus receptor binding either. The antiviral effect of GL was abolished by treatment 1 h after virus infection, whereas pre-treatment and treatment during and after virus adsorption led to a reduction in the cytopathic effect, reduced viral RNA within the cells and in the cell supernatants, and reduced viral hemagglutination titers. Detailed virus uptake analyses unambiguously demonstrated reduced virus uptake in various GL-treated cells. These observations lead to the conclusion, that the antiviral activity of GL is mediated by an interaction with the cell membrane which most likely results in reduced endocytotic activity and hence reduced virus uptake. These insights might help in the design of structurally related compounds leading to potent anti-influenza therapeutics.