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Abstract. Caffeic acid has been shown to inhibit the multiplication of influenza A virus in vitro, whereas caffeine, quinic acid and chlorogenic acid do not. Caffeic acid has also been shown to have antiviral activity against herpes simplex virus (DNA virus) and polio virus (RNA virus). In the present study, a comparison of the one-step growth curve of the influenza virus in the presence of caffeic acid with that in the absence of the reagent showed that an eclipse period of the virus multiplication in the infected cells was not affected by the reagent, while the progeny virus yield was markedly decreased in the presence of caffeic acid. In additional experiments, it was found that the addition of caffeic acid at an early time point post-infection (within 3 h post-infection) was mandatory for extensive antiviral activity, suggesting that a major target of the reagent exists in the early stages of infection. Simultaneously with the decrease in the progeny virus yield, both the virusinduced cytopathic effects and apoptotic nuclear fragmentation were markedly suppressed by the reagent, suggesting that caffeic acid suppresses, at least temporally, the degeneration of the virus-infected cells and that the observed antiviral activity is likely not the secondary result of the cytotoxic effects of the reagent. These results suggest the potential pharmacological use of caffeic acid or its derivatives as an antiviral drug against influenza A virus.

Virus infection is one of the major threats to human health and can be avoided by minimizing exposure to infectious viruses. Viral clearance of pharmaceutical products and sanitization of skin and mucosal surfaces would reduce such exposures. Even with such care, virus infection does occur, requiring effective treatments by antiviral or virucidal agents. Natural products, in particular ingredients of foods and drinks we normally consume or metabolites present in human body at low concentrations, would have advantage over synthetic drugs as antiviral agents for safety concerns. For this reason, we have been studying natural products for their effects on virus inactivation and growth. Such natural products, which we have been focusing, include gallate derivatives, caffeine present in coffee, caffeic acid present in coffee and various fruits, ascorbic and dehydroascorbic acids and a cell metabolite, arginine. Here we will review our work on antiviral and virucidal activities of these compounds and the mechanism of their antiviral and virucidal effects.