In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2.

IF 2 4区生物学 Q4 CELL BIOLOGY

Acta Naturae Pub Date : 2023-10-01 DOI:10.32607/actanaturae.26623

A N Narovlyansky, M V Filimonova, N G Tsyshkova, A V Pronin, T V Grebennikova, E V Karamov, V F Larichev, G V Kornilayeva, I T Fedyakina, I V Dolzhikova, M V Mezentseva, E I Isaeva, V V Poloskov, L S Koval, V P Marinchenko, V I Surinova, A S Filimonov, A A Shitova, O V Soldatova, A V Sanin, I K Zubashev, A V Ponomarev, V V Veselovsky, V V Kozlov, A V Stepanov, A V Khomich, V S Kozlov, S A Ivanov, P V Shegai, A D Kaprin, F I Ershov, A L Gintsburg

{"title":"In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2.","authors":"A N Narovlyansky, M V Filimonova, N G Tsyshkova, A V Pronin, T V Grebennikova, E V Karamov, V F Larichev, G V Kornilayeva, I T Fedyakina, I V Dolzhikova, M V Mezentseva, E I Isaeva, V V Poloskov, L S Koval, V P Marinchenko, V I Surinova, A S Filimonov, A A Shitova, O V Soldatova, A V Sanin, I K Zubashev, A V Ponomarev, V V Veselovsky, V V Kozlov, A V Stepanov, A V Khomich, V S Kozlov, S A Ivanov, P V Shegai, A D Kaprin, F I Ershov, A L Gintsburg","doi":"10.32607/actanaturae.26623","DOIUrl":null,"url":null,"abstract":"The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC50 = 1.06 μg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.","PeriodicalId":6989,"journal":{"name":"Acta Naturae","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10790354/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Naturae","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.32607/actanaturae.26623","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012-2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy) carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility - high activity (IC₅₀ = 1.06 μg/mL) and high selectivity index (SI = 78.6) - this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.

查看原文本刊更多论文

一种新的吲哚-3-羧酸衍生物对 SARS-CoV-2 的体外抗病毒活性。

冠状病毒病（COVID-19）大流行使人们对冠状病毒造成的威胁有了更深刻的认识，并为对这一病毒家族进行基本分析和寻找有效的抗冠状病毒药物奠定了基础。目前正在更新现有的 COVID-19 疫苗，并继续筛选用于门诊治疗的低分子量抗 COVID 候选药物。在为下一次大流行做准备的背景下，正在讨论加快开发针对其他病原体的抗病毒药物的机会和方法。2012-2015年，Tsyshkova等人合成了一组具有抗病毒活性的水溶性低分子量化合物，其化学结构与arbidol相似。其中，有一些水溶性化合物以 5-甲氧基吲哚-3-羧酸氨基烷基酯为基础。在这组相当广泛的化合物中，只有 6-溴-5-甲氧基-1-甲基-2-(1-哌啶甲基)-3-(2-二乙氨基乙氧基)羰基吲哚的二盐酸盐在体外对 SARS-CoV-2 具有可靠的抗病毒作用。浓度为 52.0 μM 时，该化合物能完全抑制 SARS-CoV-2 病毒的复制，其感染活性为 106 TCID50/mL。所分析化合物的浓度曲线表明了其作用的特异性。此外，该化合物还具有干扰素诱导活性，对 SARS-CoV-2 的尖峰蛋白（S-糖蛋白）诱导的合胞体形成的抑制率高达 89%。鉴于该化合物的合成易得性--高活性（IC50 = 1.06 μg/mL）和高选择性指数（SI = 78.6），它似乎符合开发用于 COVID-19 预防和治疗的抗病毒药物的要求。

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

Acta Naturae 农林科学-林学

CiteScore

3.50

自引率

5.00%

发文量

审稿时长

>12 weeks

期刊介绍： Acta Naturae is an international journal on life sciences based in Moscow, Russia. Our goal is to present scientific work and discovery in molecular biology, biochemistry, biomedical disciplines and biotechnology. These fields represent the most important priorities for the research and engineering development both in Russia and worldwide. Acta Naturae is also a periodical for those who are curious in various aspects of biotechnological business, innovations in pharmaceutical areas, intellectual property protection and social consequences of scientific progress. The journal publishes analytical industrial surveys focused on the development of different spheres of modern life science and technology. Being a radically new and totally unique journal in Russia, Acta Naturae is useful to both representatives of fundamental research and experts in applied sciences.