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新型 2019 年冠状病毒结构、作用机制、抗病毒药物前景及其治疗排除。

Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment.

机构信息

Centro de Bioinformática y Simulación Molecular (CBSM), Universidad de Talca, Talca, Chile.

Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research Polish Academy of Science, Warsaw, Poland.

出版信息

J Biomol Struct Dyn. 2021 Jun;39(9):3409-3418. doi: 10.1080/07391102.2020.1758788. Epub 2020 Apr 30.

Abstract

In the past two decades, the world has faced several infectious disease outbreaks. Ebola, Influenza A (H1N1), SARS, MERS, and Zika virus have had a massive global impact in terms of economic disruption, the strain on local and global public health. Most recently, the global outbreak of novel coronavirus 2019 (SARS-CoV-2) that causes COVID-19 is a newly discovered virus from the coronavirus family in Wuhan city, China, known to be a great threat to the public health systems. As of 15 April 2020, The Johns Hopkins University estimated that the COVID-19 affected more than two million people, resulting in a death toll above 130,000 around the world. Infected people in Europe and America correspond about 40% and 30% of the total reported cases respectively. At this moment only few Asian countries have controlled the disease, but a second wave of new infections is expected. Predicting inhibitor and target to the COVID-19 is an urgent need to protect human from the disease. Therefore, a protocol to identify anti-COVID-19 candidate based on computer-aided drug design is urgently needed. Thousands of compounds including approved drugs and drugs in the clinical trial are available in the literature. In practice, experimental techniques can measure the time and space average properties but they cannot be captured the structural variation of the COVID-19 during the interaction of inhibitor. Computer simulation is particularly suitable to complement experiments to elucidate conformational changes at the molecular level which are related to inhibition process of the COVID-19. Therefore, is essential tool to elucidate the phenomenon. The structure-based virtual screening computational approach will be used to filter the best drugs from the literature, the investigate the structural variation of COVID-19 with the interaction of the best inhibitor is a fundamental step to design new drugs and vaccines which can combat the coronavirus. This mini-review will address novel coronavirus structure, mechanism of action, and trial test of antiviral drugs in the lab and patients with COVID-19.

摘要

在过去的二十年中,世界经历了几次传染病爆发。埃博拉病毒、甲型流感(H1N1)、严重急性呼吸综合征(SARS)、中东呼吸综合征(MERS)和寨卡病毒都对经济造成了巨大的破坏,对当地和全球公共卫生系统造成了巨大的压力。最近,在中国武汉市发现的新型冠状病毒 2019(SARS-CoV-2)引起的 COVID-19 全球爆发是一种新型冠状病毒,被认为对公共卫生系统构成巨大威胁。截至 2020 年 4 月 15 日,约翰霍普金斯大学估计 COVID-19 已影响超过 200 万人,全球死亡人数超过 13 万。欧洲和美洲的感染者分别占总报告病例的约 40%和 30%。目前只有少数亚洲国家控制了这种疾病,但预计会出现第二波新的感染。预测 COVID-19 的抑制剂和靶标是保护人类免受该疾病侵害的当务之急。因此,迫切需要制定一种基于计算机辅助药物设计的识别抗 COVID-19 候选药物的方案。文献中包含数千种化合物,包括已批准的药物和临床试验中的药物。在实践中,实验技术可以测量时间和空间的平均性质,但不能捕捉到 COVID-19 在抑制剂相互作用过程中的结构变化。计算机模拟特别适合补充实验,以阐明与 COVID-19 抑制过程相关的分子水平的构象变化。因此,它是阐明这种现象的必要工具。将使用基于结构的虚拟筛选计算方法从文献中筛选出最佳药物,研究 COVID-19 与最佳抑制剂相互作用时的结构变化,是设计能够对抗冠状病毒的新药物和疫苗的基础步骤。这篇小型综述将介绍新型冠状病毒的结构、作用机制以及实验室和 COVID-19 患者中抗病毒药物的试验测试。

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