Prediction of repurposed drugs for treating lung injury in COVID-19.
Prediction of repurposed drugs for treating lung injury in COVID-19.
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DOI：
10.12688/f1000research.23996.1
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发表时间：
2020-01-01
期刊：
影响因子：
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通讯作者：
Garmire, Lana
中科院分区：
文献类型：
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作者：
He, Bing;Garmire, Lana
背景：冠状病毒病（COVID-19）是2019年发现的一种传染病，目前在全球范围内爆发。肺损伤伴严重呼吸衰竭是由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的COVID-19死亡的主要原因。然而，对于COVID-19引起的肺损伤和急性呼吸衰竭仍然缺乏有效的治疗。研究方法：由SARS-CoV-2的刺突蛋白引起的血管紧张素转换酶2（ACE 2）抑制是COVID-19肺损伤的最合理机制。我们进行了药物重新定位分析，以确定候选药物，逆转基因表达模式的L1000肺细胞系HCC 515与ACE 2抑制剂处理。我们通过使用死于COVID-19的患者的肺组织进行类似的生物信息学分析来确认这些候选药物。我们进一步研究了与肺损伤相关的失调基因和途径，以及基因-途径-候选药物的关系。结果如下：我们提出了两种候选药物COL-3（一种化学修饰的四环素）和CGP-60474（一种细胞周期蛋白依赖性激酶抑制剂），用于治疗COVID-19的肺损伤。进一步的生物信息学分析表明，12个显著富集的途径（P值
Background: Coronavirus disease (COVID-19) is an infectious disease discovered in 2019 and currently in outbreak across the world. Lung injury with severe respiratory failure is the leading cause of death in COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there still lacks efficient treatment for COVID-19 induced lung injury and acute respiratory failure. Methods: Inhibition of angiotensin-converting enzyme 2 (ACE2) caused by the spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. We performed drug repositioning analysis to identify drug candidates that reverse gene expression pattern in L1000 lung cell line HCC515 treated with ACE2 inhibitor. We confirmed these drug candidates by similar bioinformatics analysis using lung tissues from patients deceased from COVID-19. We further investigated deregulated genes and pathways related to lung injury, as well as the gene-pathway-drug candidate relationships. Results: We propose two candidate drugs, COL-3 (a chemically modified tetracycline) and CGP-60474 (a cyclin-dependent kinase inhibitor), for treating lung injuries in COVID-19. Further bioinformatics analysis shows that 12 significantly enriched pathways (P-value