A A Shtro1, V V Zarubaev2, O A Luzina3, D N Sokolov3, N F Salakhutdinov3. 1. Influenza Research Institute, Laboratory of Antiviral Chemotherapy, Saint-Petersburg, Russia anna.shtro@influenza.spb.ru. 2. Influenza Research Institute, Laboratory of Antiviral Chemotherapy, Saint-Petersburg, Russia. 3. Novosibirsk Institute of Organic Chemistry, Department of Medical Chemistry, Novosibirsk, Russia.
Abstract
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.
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.
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