Drug Repurposing for COVID-19 Treatment by Integrating Network Pharmacology and Transcriptomics

被引:12
作者
Liu, Dan-Yang [1 ]
Liu, Jia-Chen [2 ]
Liang, Shuang [2 ]
Meng, Xiang-He [2 ]
Greenbaum, Jonathan [3 ]
Xiao, Hong-Mei [2 ]
Tan, Li-Jun [1 ]
Deng, Hong-Wen [1 ,2 ,3 ]
机构
[1] Hunan Normal Univ, Coll Life Sci, Lab Mol & Stat Genet, Changsha 410081, Peoples R China
[2] Cent South Univ, Sch Basic Med Sci, Ctr Syst Biol Data Sci & Reprod Hlth, Changsha 410013, Peoples R China
[3] Tulane Univ, Sch Med, Deming Dept Med, Tulane Ctr Biomed Informat & Genom, New Orleans, LA 70112 USA
基金
美国国家卫生研究院;
关键词
SARS-CoV-2; COVID-19; drug repurposing; network-based pharmacology; SET ENRICHMENT ANALYSIS; PREDICTION; INFECTION; EFFICACY;
D O I
10.3390/pharmaceutics13040545
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Since coronavirus disease 2019 (COVID-19) is a serious new worldwide public health crisis with significant morbidity and mortality, effective therapeutic treatments are urgently needed. Drug repurposing is an efficient and cost-effective strategy with minimum risk for identifying novel potential treatment options by repositioning therapies that were previously approved for other clinical outcomes. Here, we used an integrated network-based pharmacologic and transcriptomic approach to screen drug candidates novel for COVID-19 treatment. Network-based proximity scores were calculated to identify the drug-disease pharmacological effect between drug-target relationship modules and COVID-19 related genes. Gene set enrichment analysis (GSEA) was then performed to determine whether drug candidates influence the expression of COVID-19 related genes and examine the sensitivity of the repurposing drug treatment to peripheral immune cell types. Moreover, we used the complementary exposure model to recommend potential synergistic drug combinations. We identified 18 individual drug candidates including nicardipine, orantinib, tipifarnib and promethazine which have not previously been proposed as possible treatments for COVID-19. Additionally, 30 synergistic drug pairs were ultimately recommended including fostamatinib plus tretinoin and orantinib plus valproic acid. Differential expression genes of most repurposing drugs were enriched significantly in B cells. The findings may potentially accelerate the discovery and establishment of an effective therapeutic treatment plan for COVID-19 patients.
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页数:16
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共 69 条
[1]  
[Anonymous], 2020, NATURE, DOI DOI 10.3892/IJMM.2020.4636
[2]  
[Anonymous], 2020, BIOLOGY-BASEL, DOI DOI 10.1016/J.CMET.2020.06.015
[3]  
[Anonymous], 2020, DRUGS, DOI DOI 10.7759/CUREUS.8069
[4]  
[Anonymous], 2020, MED HYPOTHESES, DOI DOI 10.1056/NEJMSR2005760
[5]  
[Anonymous], 1987, CRIT CARE, DOI DOI 10.2165/00003495-198733040-00002
[6]  
[Anonymous], 2018, FUTURE MED CHEM, DOI DOI 10.1016/J.VIROL.2018.06.011
[7]  
[Anonymous], 2020, COMPUT BIOL MED, DOI DOI 10.7759/CUREUS.7343
[8]  
[Anonymous], 2018, VIROLOGY, DOI DOI 10.1007/S40265-018-0927-1
[9]  
[Anonymous], 2015, Home - Clinicaltrials
[10]  
[Anonymous], 2020, AM J PHYSIOL-LUNG C, DOI DOI 10.1038/S41581-020-0279-4