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-Reference-Cited by-同舟云学术

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

Published:2024-04-04 Issue:1 Volume: Page:148-153
ISSN:2658-719X
Container-title:Problems of Particularly Dangerous Infections
language:
Short-container-title:Problemy Osobo Opasnykh Infektsii

Author:

Zaleuskaya O. S.¹,Shiryaev V. A.²,Klimochkin Yu. N.²,Semyonov S. F.¹,Rodionova L. P.¹,Klimovich O. V.¹,Liutina Ya. V.¹,Leonova M. V.²,Kras’ko A. G.¹

Affiliation:

1. Republican Scientific and Practical Center of Epidemiology and Microbiology

2. Samara State Technical University

Abstract

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.

Publisher

Russian Research Anti-Plague Institute Microbe

Reference15 articles.

1. Dinesh D.C., Chalupska D., Silhan J., Koutna E., Nencka R., Veverka V., Boura E. Structural basis of RNA recognition by the SARS-CoV-2 nucleocapsid phosphoprotein. PLoS Pathog. 2020; 16(12):e1009100. DOI: 10.1371/journal.ppat.1009100.

2. Yang H., Rao Z. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nat. Rev. Microbiol. 2021; 19(11):685–700. DOI: 10.1038/s41579-021-00630-8.

3. Giovanetti M., Benedetti F., Campisi G., Ciccozzi A., Fabris S., Ceccarelli G., Tambone V., Caruso A., Angeletti S., Zella D., Ciccozzi M. Evolution patterns of SARS-CoV-2: Snapshot on its genome variants. Biochem. Biophys. Res. Commun. 2021; 538:88–91. DOI: 10.1016/j.bbrc.2020.10.102.

4. Fam M.S., Sedky C.A., Turky N.O., Breitinger H.G., Breitinger U. Channel activity of SARS-CoV-2 viroporin ORF3a inhibited by adamantanes and phenolic plant metabolites. Sci. Rep. 2023; 13(1):5328. DOI: 10.1038/s41598-023-31764-9.

5. Wang Y., Zhang Y., Chen J., Wang M., Zhang T., Luo W., Li Y., Wu Y., Zeng B., Zhang K., Deng R., Li W. Detection of SARSCoV-2 and its mutated variants via CRISPR-Cas13-based transcription amplification. Anal. Chem. 2021; 93(7):3393–402. DOI: 10.1021/acs.analchem.0c04303.