A. Shtro, V. Zarubaev, OA Luzina, DN Sokolov, N. Salakhutdinov
{"title":"Derivatives of usnic acid inhibit broad range of influenza viruses and protect mice from lethal influenza infection","authors":"A. Shtro, V. Zarubaev, OA Luzina, DN Sokolov, N. Salakhutdinov","doi":"10.1177/2040206616636992","DOIUrl":null,"url":null,"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.","PeriodicalId":7960,"journal":{"name":"Antiviral Chemistry and Chemotherapy","volume":"57 1","pages":"92 - 98"},"PeriodicalIF":0.0000,"publicationDate":"2015-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"25","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antiviral Chemistry and Chemotherapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/2040206616636992","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 25
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.
期刊介绍:
Antiviral Chemistry & Chemotherapy publishes the results of original research concerned with the biochemistry, mode of action, chemistry, pharmacology and virology of antiviral compounds. Manuscripts dealing with molecular biology, animal models and vaccines are welcome. The journal also publishes reviews, pointers, short communications and correspondence.