A high-throughput drug screening strategy against coronaviruses.
A high-throughput drug screening strategy against coronaviruses.
复制标题
针对冠状病毒的高通量药物筛选策略
DOI：
10.1016/j.ijid.2020.12.033
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Yu Z
中科院分区：
文献类型：
--
作者：
Liu J;Li K;Cheng L;Shao J;Yang S;Zhang W;Zhou G;de Vries AAF;Yu Z
冠状病毒（CoV）的出现和重新出现持续引起全球范围内的流行病和大流行，例如新型冠状病毒SARS-CoV-2的持续爆发。由此产生的疾病，即2019年冠状病毒病（COVID-19），已迅速发展成为全球大流行病，导致严重的健康和经济负担。尽管最近公布的新型冠状病毒疫苗重新燃起了希望，但迫切满足全球对快速治疗大流行病的需求仍面临重大挑战。鉴于冠状病毒爆发的紧迫性，我们提出了一种策略，以高通量的方式筛选潜在的广谱抗冠状病毒药物，特别是针对SARS-CoV-2。由于冠状病毒的基本功能域是广泛同源的，两种类型的温和的冠状病毒，HCoV-OC 43和MHV的可用性，应该提供一个有价值的工具，快速识别有前途的药物对冠状病毒没有第三级生物学限制的缺点。将荧光素酶报告基因引入HCoV-OC 43和MHV中以指示病毒活性，因此可以通过荧光素酶活性来定量筛选药物的抗病毒效率。在结构优化后，进一步评估对HCoV-OC 43和MHV具有抗病毒活性的化合物在SARS-CoV-2中的作用。该系统允许大规模筛选化合物，以高通量方式寻找抗CoV的广谱药物，为SARS-CoV-2或其他CoV的临床管理提供潜在的替代方案。
The emergence and re-emergence of coronaviruses (CoV) continually cause circulating epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. The resultant disease, coronavirus disease 2019 (COVID-19), has rapidly developed into a worldwide pandemic, leading to severe health and economic burdens. Although the recently announced vaccines against COVID-19 has rekindled hope, there is still a major challenge to urgently meet the global need for rapid treatment of the pandemic. Given the urgency of the CoV outbreak, we propose a strategy to screen potential broad-spectrum drugs against CoV in a high-throughput manner, particularly against SARS-CoV-2. Since the essential functional domains of CoV are extensively homologous, the availability of two types of mild CoV, HCoV-OC43 and MHV, should provide a valuable tool for the rapid identification of promising drugs against CoV without the drawbacks of level three biological confinements. The luciferase reporter gene is introduced into HCoV-OC43 and MHV to indicate viral activity, and hence the antiviral efficiency of screened drugs can be quantified by luciferase activity. Compounds with antiviral activity against both HCoV-OC43 and MHV are further evaluated in SARS-CoV-2 after structural optimizations. This system allows large-scale compounds to be screened to search for broad-spectrum drugs against CoV in a high-throughput manner, providing potential alternatives for clinical management of SARS-CoV-2 or other CoV.
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影响因子：
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发表时间：
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期刊：
Nature reviews. Drug discovery
影响因子：
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