Development of New Antiviral Agents from Natural Products

The recent great advances in medical treatment and scientific technology include the many antiviral agents that have been developed and are used for treatment of infectious diseases, but such advances have also provoked the appear- ance of resistant virus strains. Therefore, the development of new antiviral agents with diverse kinds of antiviral actions is required. The search for new antiviral agents focuses on not only synthetic compounds but also natural products such as traditional medicines, dietary supplements, and functional foods, including plants, insects, animal organs, and their com- ponents. Natural products have their own metabolites, and some of the metabolites may recognize the differences between viral and host metabolisms, resulting in antiviral activity. In general, they can be obtained cheaply and may be useful re- sources to develop new antiviral agents with different antiviral actions from those of known antiviral agents. Also, natural products and their components have been demonstrated to modify immunological activities and are candidates for biological response modifiers that are effective in alleviating symptoms and reducing mortality in virus infection. The first half of this chapter introduces natural products and purified compounds that were confirmed by in vitro experiments and animal infection models to have direct antiviral activity against herpes simplex virus type 1 (HSV-1) or influenza virus. However, even if a natural product or purified component has strong antiviral activity in vitro, if it has no therapeu- tic efficacy against virus infection in an animal infection model, it is merely an inhibitor and not a medicine. The search for antiviral agents should be based on the demonstration of prophylactic and/or therapeutic efficacy at the proper dosage in animals. In the second half, we introduce a Kampo medicine, Kakkon-to, which is a biological response modifier rather than a direct antiviral agent. It is the most common cold medicine used in traditional therapy and prescribed to about 20 million people annually in Japan. We also introduce the mode of immunomodulating activity of Kakkon-to on influenza virus and HSV-1 infection and its components, which can modulate cytokine production. We hope that this chapter will be useful in verifying the antiviral therapeutic efficacy of natural products against influenza infection and helpful in encouraging development of anti-influenza virus medicines from natural products.