n -烷基和n -苄基吲哚是抗sars - cov -2药物和nsp13抑制剂。

IF 5.4 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Aurora Albano, Roberta Emmolo, Riccardo De Santis, Elisa Patacchini, Valentina Noemi Madia, Stefania Maloccu, Davide Ialongo, Giuseppe Ruggieri, Merve Arpacioglu, Luigi Scipione, Francesco Saccoliti, Donatella Amatore, Giorgia Grilli, Florigio Lista, Francesca Esposito, Enzo Tramontano, Angela Corona, Roberto Di Santo, Roberta Costi
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引用次数: 0

摘要

COVID-19大流行激发了开发针对SARS-CoV-2的治疗策略的巨大努力,从而在临床试验中对各种潜在治疗方法进行了评估。然而,当考虑到新变异的发展和抗病毒药物的局限性时,有效的治疗方法仍然难以捉摸。因此,开发针对SARS-CoV-2的抗病毒药物至关重要。在潜在的药物靶点中,SARS-CoV-2 nsp13因其在病毒复制中的关键作用而极具吸引力。为了进一步研究nsp13抑制剂的开发,本研究描述了针对SARS-CoV-2 nsp13的新型抑制剂的设计、合成和生物学评价。新设计的n -苄基吲哚衍生物在30 μM浓度下对两种酶活性都有活性,IC50可测量,而n -烷基衍生物则表现出较差的结果。有趣的是,测试的化合物阻断病毒复制,没有细胞毒性。对接研究预测它们结合到RecA2结构域的一个变构保守位点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
N-alkyl and N-benzyl indoles are anti-SARS-CoV-2 agents and nsp13 inhibitors.

COVID-19 pandemic stimulated tremendous efforts to develop therapeutic strategies targeting SARS-CoV-2, leading to the evaluation of a wide range of potential treatments in clinical trials. However, effective therapeutics remain elusive when the development of new variants and the limits of antiviral drugs is considered. Therefore, the development of antiviral drugs against SARS-CoV-2 is of paramount importance. Among potential drug targets, the SARS-CoV-2 nsp13 is highly attractive thanks to its pivotal role in viral replication. Pursuing our studies on the development of nsp13 inhibitors, in this work we describe the design, synthesis, and biological evaluation of novel inhibitors targeting SARS-CoV-2 nsp13. The newly designed N-benzyl indole derivatives were active against both enzymatic activities showing measurable IC50 under 30 μM concentration, while N-alkyl derivatives showed less promising results. Interestingly, the tested compounds blocked viral replication with no cytotoxicity. Docking studies predicted their binding into an allosteric conserved site located in the RecA2 domain.

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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