Antiviral Mechanism of Action of Epigallocatechin-3-O-gallate and Its Fatty Acid Esters

Epigallocatechin-3-O-gallate (EGCG) is the major catechin component of green tea (Cameria sinensis), and is known to possess antiviral activities against a wide range of DNA viruses and RNA viruses. However, few studies have examined chemical modifications of EGCG in terms of enhanced antiviral efficacy. This paper discusses which steps of virus infection EGCG interferes with, citing previous reports. EGCG appears most likely to inhibits the early stage of infections, such as attachment, entry, and membrane fusion, by interfering with viral membrane proteins. According to the relationships between structure and antiviral activity of catechin derivatives, the 3-galloyl and 5′-OH group of catechin derivatives appear critical to antiviral activities. Enhancing the binding affinity of EGCG to virus particles would thus be important to increase virucidal activity. We propose a newly developed EGCG-fatty acid derivative in which the fatty acid on the phenolic hydroxyl group would be expected to increase viral and cellular membrane permeability. EGCG-fatty acid monoesters showed improved antiviral activities against different types of viruses, probably due to their increased affinity for virus and cellular membranes. Our study promotes the application of EGCG-fatty acid derivatives for the prevention and treatment of viral infections

Sialyllactose-Modified Three-Way Junction DNA as Binding Inhibitor of Influenza Virus Hemagglutinin

Sialic acid present on the cell surface is recognized by hemagglutinin (HA) on the influenza virus in the first step of infection. Therefore, a compound that can efficiently interfere with the interaction between sialic acid and HA might inhibit infection and allow detection of the influenza virus. We focused on the spatial arrangement of sialic acid binding sites on HA and developed 2,3-sialyllactose (2,3-SL)-modified three-way junction (3WJ) DNA molecules with a topology similar to that of sialic acid binding sites. 3WJ DNA with three 2,3-SL residues on each DNA strand showed (8.0 × 10⁴)-fold higher binding affinity for influenza virus A/Puerto Rico/08/34 (H1N1) compared to the 2,3-SL. This result indicated that the glycocluster effect due to clustering on one DNA arm and optimal spatial arrangement of the 3WJ DNA improved the weak interactions between a sialic acid and its binding site on HA. This 3WJ DNA compound has possible application as an inhibitor of influenza infection and for virus sensing