Molecular and Genetic Bases of Inhibition of Tick-Borne Encephalitis Virus Replication by Eprosartan and Ribavirin
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ular and Genetic Bases of Inhibition of Tick-Borne Encephalitis Virus Replication by Eprosartan and Ribavirin G. N. Leonova, O. S. Maistrovskaya, and V. A. Lubova
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 7, pp. 66-71, July, 2020 Original article submitted April 14, 2020 The antiviral activity of eprosartan (compound selected in silico) towards highly and lowvirulent strains of tick-borne encephalitis virus was compared in vitro with activity of ribavirin. Study of the cytopathogenic activity of the virus on SPEV cells by ELISA, IFAT, and PCR showed similar results: both substances (eprosartan and ribavirin) promoted elimination of tick-borne encephalitis virus. Ribavirin exhibited intracellular inhibition towards both strains: the selectivity index for highly virulent Dal’negorsk strain was 160, for low-virulent Primorye-437 strain — 113. Eprosartan inhibited intracellular replication of Dal’negorsk strain (13.7) and less so that of Primorye-437 strain (2.9). The efficiency of virtual screening of the ligand (eprosartan) was demonstrated for highly virulent, but not low virulent tick-borne encephalitis strain. Key Words: tick-borne encephalitis virus (TBE); ribavirin; eprosartan; mechanisms of virus inhibition The list of effective drugs with antiviral activity is extremely short. Detection of functionally significant target protein sites suggests identification of chemical compounds — candidate antiviral drugs. In the NS2B/ NS3 complex the interface between NS3 protease and NS2B cofactor, described previously [10], is identified as a site of this kind, which has been also detected in tick-borne encephalitis (TBE) virus [9]. Due to modern virtual screening methods, combined with the molecular docking method, it is now possible to detect inhibitors of TBE virus target proteins. Estimations of virtual screening of NS3 protease and NS5 polymerase structure were used for Zika virus, sensitive to antiviral activity of Teveten; these results can be also extrapolated to TBE virus and, presumably, to other representatives of Flavivirus genus [5]. These data gave us grounds to study the inhibitory activity of G. P. Somov Institute of Epidemiology and Microbiology, Vladivostok, Russia. Address for correspondence: [email protected]. G. N. Leonova
Teveten towards TBE strains of different virulence in comparison with a well-known and well-studied drug ribavirin, exhibiting antiviral activity towards many RNA and DNA pathogenic viruses [1,3,4]. We study in vitro the antiviral activity of eprosartan compound, selected in silico, towards highly and low-virulent TBE strains of the Far-Eastern subtype in comparison with ribavirin.
MATERIALS AND METHODS Teveten in tablets, containing 600 mg active substance eprosartan (Mylan Laboratories SAS), and ribavirin in capsules, containing 200 mg active ribavirin substance (Vertex), were used in the study. The initial solutions of eprosartan (60 mg/ml) and ribavirin (100 mg/ml) were prepared in DMSO (PanEco) and then diluted in medium 199. Swine e
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