最近爆发的COVID-19已成为全球健康问题。目前没有用于治疗或预防这种致命疾病的有效治疗策略和疫苗。目前的研究旨在通过一种计算药物再利用的方法,为COVID-19确定有希望的治疗方案。
在这项研究中,我们关注差异表达基因(DEGs),在SARS-CoV-2感染的细胞系中检测到,包括“原代人肺上皮细胞系NHBE”和“转化的肺泡细胞系A549”。接下来,识别的DEGs用于连接图(CMap)分析,以识别作用相似的候选治疗药物.此外,为了解释DEG列表,进行途径富集和蛋白质网络分析。基因根据其生物学功能分为易于解释的途径,与随机预期相比,测试了每个途径的过度表达。
结果表明兰索拉唑的有效性,叶酸,磺胺间甲氧嘧啶,Tolnaftate,双氯芬胺,卤奈德,沙奎那韦,甲硝唑,Ebselen,利多卡因和苯佐卡因,组蛋白去乙酰化酶(HDAC)抑制剂,热休克蛋白90(HSP90)抑制剂,和许多其他临床批准的药物作为对抗COVID-19爆发的强效药物。
制造新药仍然是一个漫长的过程,因此,药物再利用的方法提供了对这种大流行可能有帮助的治疗方法的见解。在这项研究中,还进行了途径富集和蛋白质网络分析,根据以前的研究,已经研究了从CMap分析中获得的一些药物的有效性。
The recent outbreak of COVID-19 has become a global health concern. There are currently no effective treatment strategies and vaccines for the treatment or prevention of this fatal disease. The current
study aims to determine promising treatment options for the COVID-19 through a computational drug repurposing approach.
In this
study, we focus on differentially expressed genes (DEGs), detected in SARS-CoV-2 infected cell lines including \"the primary human lung epithelial cell line NHBE\" and \"the transformed lung alveolar cell line A549\". Next, the identified DEGs are used in the connectivity map (CMap) analysis to identify similarly acting therapeutic candidates. Furthermore, to interpret lists of DEGs, pathway enrichment and protein network analysis are performed. Genes are categorized into easily interpretable pathways based on their biological functions, and overrepresentation of each pathway is tested in comparison to what is expected randomly.
The results suggest the effectiveness of lansoprazole, folic acid, sulfamonomethoxine, tolnaftate, diclofenamide, halcinonide, saquinavir, metronidazole, ebselen, lidocaine and benzocaine, histone deacetylase (HDAC) inhibitors, heat shock protein 90 (HSP90) inhibitors, and many other clinically approved drugs as potent drugs against COVID-19 outbreak.
Making new drugs remain a lengthy process, so the drug repurposing approach provides an insight into the therapeutics that might be helpful in this pandemic. In this
study, pathway enrichment and protein network analysis are also performed, and the effectiveness of some drugs obtained from the CMap analysis has been investigated according to previous researches.