Discovery of New Ginsenol-Like Compounds with High Antiviral Activity
Aleksandrina S. Volobueva,
Olga I. Yarovaya,
Marina V. Kireeva,
Sophia S. Borisevich,
Kseniya S. Kovaleva,
Iliya Ya. Mainagashev,
Yuri V. Gatilov,
Margarita G. Ilyina,
Vladimir V. Zarubaev,
Nariman F. Salakhutdinov
Affiliations
Aleksandrina S. Volobueva
Laboratory of Experimental Virology Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russia
Olga I. Yarovaya
Department of Medicinal Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, 630090 Novosibirsk, Russia
Marina V. Kireeva
Biology Department, St. Petersburg State University, 7/9 Universitetskaya Nab., 199034 St. Petersburg, Russia
Sophia S. Borisevich
Laboratory of Chemical Physics, Ufa Institute of Chemistry Ufa Federal Research Center, 71 Pr. Oktyabrya, 450078 Ufa, Russia
Kseniya S. Kovaleva
Department of Medicinal Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, 630090 Novosibirsk, Russia
Iliya Ya. Mainagashev
Department of Medicinal Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, 630090 Novosibirsk, Russia
Yuri V. Gatilov
Department of Medicinal Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, 630090 Novosibirsk, Russia
Margarita G. Ilyina
Laboratory of Chemical Physics, Ufa Institute of Chemistry Ufa Federal Research Center, 71 Pr. Oktyabrya, 450078 Ufa, Russia
Vladimir V. Zarubaev
Laboratory of Experimental Virology Pasteur Institute of Epidemiology and Microbiology, 14 Mira Str., 197101 St. Petersburg, Russia
Nariman F. Salakhutdinov
Department of Medicinal Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentiev Ave. 9, 630090 Novosibirsk, Russia
A number of framework amides with a ginsenol backbone have been synthesized using the Ritter reaction. We named the acetamide as Ginsamide. A method was developed for the synthesis of the corresponding amine and thioacetamide. The new compounds revealed a high activity against H1N1 influenza, which was confirmed using an animal model. Biological experiments were performed to determine the mechanism of action of the new agents, a ginsamide-resistant strain of influenza virus was obtained, and the pathogenicity of the resistant strain and the control strain was studied. It was shown that the emergence of resistance to Ginsamide was accompanied by a reduction in the pathogenicity of the influenza virus.
