基于amicoumacin的前药开发方法

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL

Bulletin of Russian State Medical University Pub Date : 2022-12-30 DOI:10.24075/brsmu.2022.073

VI Shmygarev, YuA Prokopenko, S. Terekhov, MYu Zakharova, M. Dubinnyi, I. Smirnov, IV Yampolsky, A. Tsarkova

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引用次数: 0

摘要

由SARS-CoV-2病毒引起的冠状病毒病COVID-19具有高度传染性，发病率很高。为COVID-19患者提供护理需要开发新型抗病毒药物。本研究的目的是利用抗生素Amicoumacin a (Ami)开发一种治疗冠状病毒疾病的前药，其作用机制基于翻译抑制。SARS-CoV-2主要蛋白酶对失活前药的酶解可导致活性Ami分子的释放，从而抑制受感染细胞中的蛋白质生物合成。为了验证所提出的假设，进行了Amicoumacin a的失活类似物的五阶段合成。其与SARS-CoV-2重组蛋白酶MPro的体外测试显示水解率低。进一步优化SARS-CoV-2 MPro蛋白酶识别的失活类似物的肽片段可能导致蛋白水解和Amicoumacin A的释放增加。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Amicoumacin-based prodrug development approach

Coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, is highly contagious and has a severe morbidity. Providing care to patients with COVID-19 requires the development of new types of antiviral drugs. The aim of this work is to develop a prodrug for the treatment of coronavirus disease using the antibiotic Amicoumacin A (Ami), the mechanism of action of which is based on translation inhibition. Enzymatic hydrolysis of an inactivated prodrug by the SARS-CoV-2 main protease can lead to the release of the active Ami molecule and, as a consequence, the suppression of protein biosynthesis in infected cells. To test the proposed hypothesis, a five-stage synthesis of an inactivated analogue of Amicoumacin A was carried out. Its in vitro testing with the SARS-CoV-2 recombinant protease MPro showed a low percentage of hydrolysis. Further optimization of the peptide fragment of the inactivated analog recognized by the SARS-CoV-2 MPro protease may lead to an increase in proteolysis and the release of Amicoumacin A.

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来源期刊

Bulletin of Russian State Medical University MEDICINE, GENERAL & INTERNAL-

CiteScore

0.80

自引率

0.00%

发文量

期刊介绍： Bulletin of Russian State Medical University (Bulletin of RSMU, ISSN Print 2500–1094, ISSN Online 2542–1204) is a peer-reviewed medical journal of Pirogov Russian National Research Medical University (Moscow, Russia). The original language of the journal is Russian (Vestnik Rossiyskogo Gosudarstvennogo Meditsinskogo Universiteta, Vestnik RGMU, ISSN Print 2070–7320, ISSN Online 2070–7339). Founded in 1994, it is issued once every two months publishing articles on clinical medicine and medical and biological sciences, first of all oncology, neurobiology, allergy and immunology, medical genetics, medical microbiology and infectious diseases. Every issue is thematic. Deadlines for manuscript submission are announced in advance. The number of publications on topics in spite of the issue topic is limited. The journal accepts only original articles submitted by their authors, including articles that present methods and techniques, clinical cases and opinions. Authors must guarantee that their work has not been previously published elsewhere in whole or in part and in other languages and is not under consideration by another scientific journal. The journal publishes only one review per issue; the review is ordered by the editors.