Polyphenolic compound catechins ((-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin (EGC)) from green tea were evaluated for their ability to inhibit influenza virus replication in cell culture and for potentially direct virucidal effect.
Among the test compounds, the EGCG and ECG were found to be potent inhibitors of influenza virus replication in MDCK cell culture and this effect was observed in all influenza virus subtypes tested, including A/H1N1, A/H3N2 and B virus.
The 50% effective inhibition concentration (EC50) of EGCG, ECG, and EGC for influenza A virus were 22-28, 22-40 and 309-318 microM, respectively. EGCG and ECG exhibited hemagglutination inhibition activity, EGCG being more effective. However, the sensitivity in hemagglutination inhibition was widely different among three different subtypes of influenza viruses tested. Quantitative RT-PCR analysis revealed that, at high concentration, EGCG and ECG also suppressed viral RNA synthesis in MDCK cells whereas EGC failed to show similar effect. Similarly, EGCG and ECG inhibited the neuraminidase activity more effectively than the EGC. The results show that the 3-galloyl group of catechin skeleton plays an important role on the observed antiviral activity, whereas the 5'-OH at the trihydroxy benzyl moiety at 2-position plays a minor role.
The results, along with the HA type-specific effect, suggest that the antiviral effect of catechins on influenza virus is mediated not only by specific interaction with HA, but altering the physical properties of viral membrane.
Green tea catechins have been reported to inhibit proteases involved in cancer metastasis and infection by influenza virus and HIV. To date there are no effective anti-adenoviral therapies. Consequently, we studied the effect of green tea catechins, and particularly the predominant component, epigallocatechin-3-gallate (EGCG), on adenovirus infection and the viral protease adenain, in cell culture.
Adding EGCG (100 microM) to the medium of infected cells reduced virus yield by two orders of magnitude, giving and IC(50) of 25 microM and a therapeutic index of 22 in Hep2 cells. The agent was the most effective when added to the cells during the transition from the early to the late phase of viral infection suggesting that EGCG inhibits one or more late steps in virus infection. One of these steps appears to be virus assembly because the titer of infectious virus and the production of physical particles was much more affected than the synthesis of virus proteins. Another step might be the maturation cleavages carried out by adenain. Of the four catechins tested on adenain, EGCG was the most inhibitory with an IC(50) of 109 microM, compared with an IC(50) of 714 microM for PCMB, a standard cysteine protease inhibitor. EGCG and different green teas inactivated purified adenovirions with IC(50) of 250 and 245-3095, respectively.
We conclude that the anti-adenoviral activity of EGCG manifests itself through several mechanisms, both outside and inside the cell, but at effective drug concentrations well above that reported in the serum of green tea drinkers.
Song JM, Lee KH, Seong BL. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res. 2005 Nov;68(2):66-74. Epub 2005 Aug 9.
Department of Biotechnology, College of Engineering, Yonsei University, 134, Shinchon-dong, Seodaemun-gu, Seoul 120-749, South Korea.
Weber JM, Ruzindana-Umunyana A, Imbeault L, Sircar S. Inhibition of adenovirus infection and adenain by green tea catechins. Antiviral Res. 2003 Apr;58(2):167-73.
Departement de Microbiologie et d'Infectiologie, Faculte de Medecine, Universite de Sherbrooke, Que, Sherbrooke, Canada J1H 5N4. firstname.lastname@example.org