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

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

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引用次数: 0

摘要

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。

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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

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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Problems of Particularly Dangerous Infections

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