Cage structures – inhibitors of flavivirus p7 ion channelтезисы доклада

Дата последнего поиска статьи во внешних источниках: 10 июня 2020 г.

Работа с тезисами доклада

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1. Полный текст Klimochkin-Mendeleev2019_5_81.pdf 299,1 КБ 20 декабря 2019 [genie@qsar.chem.msu.ru]

[1] Cage structures – inhibitors of flavivirus p7 ion channel / Y. N. Klimochkin, V. A. Shiryaev, M. V. Leonova et al. // ХХI Mendeleev Congress on General and Applied Chemistry, Saint Petersburg, Russia, 9-13 September 2019. — Vol. 5. — Saint Petersburg, Russia, 2019. — P. 81–81. Cage fragments are relatively often found in the structure of medicines, including the well-known antiviral drugs. Hepatitis C virus is one of the most dangerous viruses. Currently, there are direct-acting antivirals (DAA) for hepatitis C, their targets are NS3 / 4A protease, NS5A replication activator and NS5B polymerase, however their successful application is complicated due to the high variability of the virus and drug resistance. There is another potential target - the viral protein p7, which functions as an ion channel. The development of potential inhibitors of hepatitis C virus reproduction was performed for the p7 proteins produced by viruses of the most common genotypes Gt1a, Gt1b, Gt2a and Gt2b (protein primary structures UniProt: P26664, P26663, P26660, P26661, respectively). The three-dimensional structures of ion channels were obtained using molecular dynamics. Molecular docking of more than 800 structures revealed compounds potentially active against hepatitis C virus and bovine diarrhea virus (BVDV). Based on the results obtained, a series of adamantane and homoadamantane derivatives were synthesized. Testing of antiviral activity was carried out in the SRC VB Vector. Most of the synthesized compounds showed pronounced antiviral activity in vitro against bovine diarrhea virus as a surrogate model of the hepatitis C virus, one of the compounds showed high activity and can be used as a leader for further research.

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