Derivatives of usnic acid inhibit broad range of influenza viruses and protect mice from lethal influenza infection

Background Influenza is a disease of significant morbidity and mortality, the number of anti-influenza drugs is small; many of them stimulate the appearance of resistant strains. In this work, we demonstrate activity of some usnic acid (UA) derivatives against influenza virus in vitro and in vivo. Methods Organic synthesis was used to prepare compounds. Antiviral activity of the compounds in vitro was evaluated by their ability to decrease the virus titer on Madin–Darby Canine Kidney cells. In vivo activity was evaluated by decrease of mortality and index of protection. Results Compounds were tested against a broad spectrum of influenza virus strains and showed activity against all used strains. One compound, [5] (valine enamine of UA), also significantly reduced lethality of infected animals and does not give rise to the appearance of resistant strains. Additional studies showed that hepatotoxicity of compound [5] is reduced comparatively to UA. Conclusion Our results suggest that valine enamine of UA could be a potential candidate for the development of a new anti-influenza therapy.