论文标题
计算药物重新定位和阐明化合物对SARS-COV-2的作用机理
Computational Drug Repositioning and Elucidation of Mechanism of Action of Compounds against SARS-CoV-2
论文作者
论文摘要
COVID-19危机要求从生物医学研究的所有领域进行快速反应。传统的药物开发涉及耗时的管道，这些管道与在健康和经济紧急情况下识别有效疗法的迫切需要冲突。药物重新定位，即发现已经批准用于不同治疗环境的药物的新临床应用，可以提供有效的捷径，以及时将Covid-19的治疗带到床边。此外，计算方法可以帮助进一步加速过程。在这里，我们介绍了基于转录组学数据的计算药物重新定位工具的应用，以识别能够抵消SARS-COV-2感染的药物，并提供有关其作用方式的见解。我们认为，粘液溶剂和HDAC抑制剂需要进一步研究。此外，我们发现DNA不匹配修复途径受到对SARS-COV-2感染的实验性体外活性的药物的强烈调节。完整的结果和方法均可公开使用。
The COVID-19 crisis called for rapid reaction from all the fields of biomedical research. Traditional drug development involves time consuming pipelines that conflict with the urgence of identifying effective therapies during a health and economic emergency. Drug repositioning, that is the discovery of new clinical applications for drugs already approved for different therapeutic contexts, could provide an effective shortcut to bring COVID-19 treatments to the bedside in a timely manner. Moreover, computational approaches can help accelerate the process even further. Here we present the application of computational drug repositioning tools based on transcriptomics data to identify drugs that are potentially able to counteract SARS-CoV-2 infection, and also to provide insights on their mode of action. We believe that mucolytics and HDAC inhibitors warrant further investigation. In addition, we found that the DNA Mismatch repair pathway is strongly modulated by drugs with experimental in vitro activity against SARS-CoV-2 infection. Both full results and methods are publicly available.
