Flavivirus Reproduction Inhibitors

• Molecular dynamics simulations of flavivirus envelope proteins, analysis of intrinsic determinants of virion properties
• Design of small molecule antiviral compounds against tick-borne encephalitis, dengue fever, and other diseases caused by flaviviruses

Flaviviruses are the cause of dangerous infectious diseases such as dengue fever, West Nile fever, yellow fever and tick-borne encephalitis.

Based on the virtual screening results, we have developed small molecule compounds having record activity against tick-borne encephalitis virus (IC₅₀ 0.07 uM).

Publications

• L. I. Kozlovskaya, A. D. Golinets, A. A. Eletskaya, A. A. Orlov, V. A. Palyulin, S. N. Kochetkov, L. A. Alexandrova, D. I. Osolodkin. Selective inhibition of Enterovirus A species members’ reproduction by furano[2,3-d]pyrimidine nucleosides revealed by antiviral activity profiling against (+)ssRNA viruses. ChemistrySelect, 2018, 3, 2321–2325.
• A. A. Orlov, M. S. Drenichev, V. E. Oslovsky, N. N. Kurochkin, P. N. Solyev, L. I. Kozlovskaya, V. A. Palyulin, G. G. Karganova, S. N. Mikhailov, D. I. Osolodkin. New tools in nucleoside toolbox of tick-borne encephalitis virus reproduction inhibitors. Bioorganic & Medicinal Chemistry Letters,  2017, 27, 1267–1273.
• A. V. Aralov, G. V. Proskurin, A. A. Orlov, L. I. Kozlovskaya, A. A. Chistov, S. V. Kutyakov, G. G. Karganova, V. A. Palyulin, D. I. Osolodkin, V. A. Korshun. Perylenyltriazoles inhibit reproduction of enveloped viruses. European Journal of Medicinal Chemistry,  2017, 138, 293–299.
• A. A. Orlov, A. A. Chistov, L. I. Kozlovskaya, A. V. Ustinov, V. A. Korshun, G. G. Karganova, D. I. Osolodkin. Rigid amphipathic nucleosides suppressing reproduction of tick-borne encephalitis virus. MedChemComm,  2016, 7, 495–499.
• K. N. Sedenkova, E. V. Dueva, E. B. Averina, Y. K. Grishin, D. I. Osolodkin, L. I. Kozlovskaya, V. A. Palyulin, E. N. Savelyev, B. S. Orlinson, I. A. Novakov, G. M. Butov, T. S. Kuznetsova, G. G. Karganova, N. S. Zefirov. Synthesis and Assessment of 4-Aminotetrahydroquinazoline Derivatives as Tick-Borne Encephalitis Virus Reproduction Inhibitors. Organic & Biomolecular Chemistry, 2015, 13, 3406–3415.
• E. V. Dueva, D. I. Osolodkin, L. I. Kozlovskaya, V. A. Palyulin, V. M. Pentkovski, N. S. Zefirov. Interaction of Flaviviruses with Reproduction Inhibitors Binding in β-OG Pocket: Insights from Molecular Dynamics Simulations. Molecular Informatics, 2014, 33, 695–708.
• D. I. Osolodkin, L. I. Kozlovskaya, E. V. Dueva, V. V. Dotsenko, Y. V. Rogova, K. A. Frolov, S. G. Krivokolysko, E. G. Romanova, A. S. Morozov, G. G. Karganova, V. A. Palyulin, V. M. Pentkovski, N. S. Zefirov. Inhibitors of Tick-Borne Flavivirus Reproduction from Structure-Based Virtual Screening. ACS Medicinal Chemistry Letters, 2013, 4, 869–874.
• D. I. Osolodkin, L. I. Kozlovskaya, V. A. Palyulin, V. M. Pentkovski, G. G. Karganova, N. S. Zefirov. A Molecular Model and Monte Carlo Simulation of Flavivirus Envelope Building Block. Biochemical and Biophysical Research Communications, 2012, 425, 207–211.
• L. I. Kozlovskaya, D. I. Osolodkin, A. S. Shevtsova, L. I. Romanova, Y. V. Rogova, T. I. Dzhivanian, V. N. Lyapustin, G. P. Pivanova, A. P. Gmyl, V. A. Palyulin, G. G. Karganova. GAG-Binding Variants of Tick-Borne Encephalitis Virus. Virology, 2010, 398, 262–272.