ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

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Abstract

Influenza is a highly contagious human disease. In the course of use of antiviral drugs drug-resistant strains of the virus are formed, resulting in reduced efficiency of the chemotherapy. The review describes the biological activity of glycirrhetinic (GLA) and glycirrhizic (GA) acids in terms of their use as a therapeutic agent for viral infections. So, these compounds are against a broad spectrum of viruses, including herpes, corona-, alphaand flaviviruses, human immunodeficiency virus, vaccinia virus, poliovirus type I, vesicular stomatitis virus and influenza A virus. These data indicate that anti-viral effect of these compounds is due to several types of activity — direct antiviral effects, effects on cellular proand anti-viral and immunomodulating pathways, in particular by activation of innate immunity system. GA interferes with early steps of the viral reproductive cycle such as virus binding to its receptor, the absorption of the virus by endocytosis or virus decapsidation in the cytoplasm. This is due to the effect of GA-induced reduction of membrane fluidity. Thus, one mechanism for the antiviral activity of GA is that GA molecule increases the rigidity of cellular and viral membranes after incorporation in there. This results in increasing of energy threshold required for the formation of negative curvature at the fusion zones, as well as difficult lateral migration of the virus-receptor complexes. In addition, glycyrrhizin prevents interaction of viral nucleoprotein with cellular protein HMGB1, which is necessary for the viral life cycle. Glycyrrhizin also inhibits the induction of oxidative stress during influenza infection, exhibiting antioxidant properties, which leads to a reduction of virus-induced production of cytokines/chemokines, without affecting the replication of the virus. A wide spectrum of biological activity and effect on various aspects of the viral pathogenesis substantiate the effect of GA and GLA as a component of a complex antiviral therapy. A combination of antiviral mechanisms makes GA and GLA unique means capable of providing an antiviral effect in many types of viral pathologies that emphasizes their prospects as a component of comprehensive antiviral therapy. Further research in the field of optimization of their application may lead to the development of new antiviral drugs and effective schemes of their combined application.

About the authors

V. V. Zarubaev

Research Institute of Influenza, 197376, Russian Federation, St. Petersburg, Professor Popov str., 15/17

Author for correspondence.
Email: zarubaev@influenza.spb.ru

PhD (Biology), Leading Researcher, Department of Pre-Clinical Trials, Research Institute of Influenza, St. Petersburg, Russian Federation

Russian Federation

V. B. Anikin

Research Institute of Influenza, 197376, Russian Federation, St. Petersburg, Professor Popov str., 15/17

Email: fake@neicon.ru

Senior Researcher, Department of Pre-Clinical Trials, Research Institute of Influenza, St. Petersburg, Russian Federation

Russian Federation

V. S. Smirnov

MBRD “Cytomed”, St. Petersburg, Russian Federation

Email: fake@neicon.ru

PhD, MD (Medicine), Head Researcher, MBRD “Cytomed”, St. Petersburg, Russian Federation

Russian Federation

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