Проблемы особо опасных инфекций (Apr 2024)

Assessment of the Impact of Polycyclic Derivatives of the Frame Series on the Replicative Properties of the SARS-CoV-2 Virus in an <I>in vitro</I> Experiment

  • O. S. Zaleuskaya,
  • V. A. Shiryaev,
  • Yu. N. Klimochkin,
  • S. F. Semyonov,
  • L. P. Rodionova,
  • O. V. Klimovich,
  • Ya. V. Liutina,
  • M. V. Leonova,
  • A. G. Kras’ko

DOI
https://doi.org/10.21055/0370-1069-2024-1-148-153
Journal volume & issue
Vol. 0, no. 1
pp. 148 – 153

Abstract

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The aim of the work was to determine the cytotoxicity and the influence of polycyclic derivatives of the framework series on the replicative properties of the SARS-CoV-2 virus in Vero-E6 cell culture in vitro. Materials and methods. The virus inhibiting effect of 50 adamantane and bicyclo[3.3.1]nonane derivatives with carbocyclic and heterocyclic substituents was investigated. The studies were carried out on Vero-E6 cell culture by assessing the cytopathic effect of the virus. The impact of the compounds on the replicative properties of the SARS-CoV-2 virus was estimated by the decrease in virus titer in the presence of the compounds compared to the control. Based on the virus titer values in the presence of a series of successively decreasing concentrations of the compound, the 50 % effective concentration was calculated.Results and discussion. A study of polycyclic derivatives of the framework series has identified two compounds with antiviral properties against the SARS-CoV-2 virus. Among bicyclo[3.3.1]nonane derivatives containing heterocyclic fragments, compound No. 15144 has showed an inhibitory effect against the SARS-CoV-2 virus. The protective effect of the compound was manifested in maximum tolerable concentration (MTC) (70.0 μg/ml) and ½ MTC (35.0 µg/ml). A decrease in virus titers under the influence of MTC by 0.95 lg TCD50/ml, in ½ MTC (35.0 μg/ml) – by 0.35 lg TCID50/ml has been detected. The effective concentration (EC50) value of the compound No. 15144 was 64.0 μg/ml, the MTC/EC50 ratio was 1.09. Compound No. 14838 (adamantane derivative containing carbocyclic fragments) had less pronounced antiviral activity. As a result of research, it has been established that sample No. 14838 at a dose of MTC (45.0 μg/ml) reduces the infectious titer by 0.78 lg TCD50/ml, in ½ MTC (22.5 μg/ml) by 0.15 lg TCD50/ml compared to the control. The EC50 value of compound No. 14838 was 37.0 μg/ml, the MTC/EC50 ratio was 1.22.

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