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

Problems of Particularly Dangerous Infections Pub Date : 2024-04-04 DOI:10.21055/0370-1069-2024-1-148-153

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

{"title":"Assessment of the Impact of Polycyclic Derivatives of the Frame Series on the Replicative Properties of the SARS-CoV-2 Virus in an in vitro Experiment","authors":"O. S. Zaleuskaya, V. A. Shiryaev, Yurii Klimochkin, S. F. Semyonov, L. P. Rodionova, O. V. Klimovich, Ya. V. Liutina, M. V. Leonova, A. G. Kras’ko","doi":"10.21055/0370-1069-2024-1-148-153","DOIUrl":null,"url":null,"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.","PeriodicalId":516710,"journal":{"name":"Problems of Particularly Dangerous Infections","volume":"42 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Problems of Particularly Dangerous Infections","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21055/0370-1069-2024-1-148-153","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

在体外实验中评估框架系列多环衍生物对 SARS-CoV-2 病毒复制特性的影响

这项工作的目的是确定框架系列多环衍生物的细胞毒性及其对 Vero-E6 细胞体外培养 SARS-CoV-2 病毒复制特性的影响。材料和方法研究了 50 种带有碳环和杂环取代基的金刚烷和双环[3.3.1]壬烷衍生物对病毒的抑制作用。研究是在 Vero-E6 细胞培养中通过评估病毒的细胞病理效应进行的。化合物对 SARS-CoV-2 病毒复制特性的影响是通过与对照组相比，存在化合物时病毒滴度的降低来估算的。根据一系列浓度依次降低的化合物存在时的病毒滴度值，计算出 50% 的有效浓度。对框架系列多环衍生物的研究发现了两种对 SARS-CoV-2 病毒具有抗病毒特性的化合物。在含有杂环片段的双环[3.3.1]壬烷衍生物中，15144 号化合物对 SARS-CoV-2 病毒有抑制作用。该化合物的保护作用在最大耐受浓度（MTC）（70.0 μg/ml）和 ½ MTC（35.0 µg/ml）下均有体现。在 MTC 的影响下，病毒滴度下降了 0.95 lg TCD50/ml，在 ½ MTC（35.0 μg/ml）的影响下，病毒滴度下降了 0.35 lg TCID50/ml。15144 号化合物的有效浓度（EC50）值为 64.0 μg/ml，MTC/EC50 比率为 1.09。14838 号化合物（含有碳环片段的金刚烷衍生物）的抗病毒活性较弱。研究结果表明，与对照组相比，14838 号样品在 MTC（45.0 μg/ml）剂量下可降低感染滴度 0.78 lg TCD50/ml，在 ½ MTC（22.5 μg/ml）剂量下可降低感染滴度 0.15 lg TCD50/ml。14838 号化合物的 EC50 值为 37.0 μg/ml，MTC/EC50 比率为 1.22。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Problems of Particularly Dangerous Infections

自引率

0.00%

发文量