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Antiviral effect of catechins in green tea on
influenza virus. 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. 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. |
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