Wang Zhihan, Guo Kai, Gao Pan, Pu Qinqin, Wu Min, Li Changlong, Hur Junguk
West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA.
ArXiv. 2020 May 16:arXiv:2005.07856v2.
Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. There is no specific drug for COVID-19, highlighting the urgent need for the development of effective therapeutics. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating the gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from mild and severe COVID-19 patients. We identified 281 FDA-approved drugs that have the potential to be effective against SARS-CoV-2 infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus. In conclusion, we have identified a list of repurposable anti-SARS-CoV-2 drugs using a systems biology approach.
2019年冠状病毒病（COVID-19）已经影响了全球人类生活的几乎方方面面，对人类健康构成了巨大威胁。目前尚无针对COVID-19的特效药物，这凸显了开发有效治疗方法的迫切需求。为了确定可能具有重新利用价值的药物，我们采用了一种系统方法，通过将基于综合网络的细胞特征库项目中化学物质的基因表达扰动数据与来自轻症和重症COVID-19患者的公开单细胞RNA测序数据集相结合，从美国食品药品监督管理局（FDA）批准的药物和临床前小分子化合物中挖掘候选药物。我们鉴定出281种FDA批准的可能对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染有效的药物，其中16种目前正在进行临床试验以评估其对COVID-19的疗效。我们通过实验测试了酪氨酸磷酸化抑制剂AG-1478和布雷菲德菌素A对单链核糖核酸（ssRNA）病毒甲型流感病毒复制的抑制作用。总之，我们利用系统生物学方法确定了一份可重新利用的抗SARS-CoV-2药物清单。
