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  • 标题:Rational drug repositioning for coronavirus-associated diseases using directional mapping and side-effect inference
  • 本地全文:下载
  • 作者:Jianhua Wang ; Jiaojiao Liu ; Menghan Luo
  • 期刊名称:iScience
  • 印刷版ISSN:2589-0042
  • 出版年度:2022
  • 卷号:25
  • 期号:11
  • 页码:1-20
  • DOI:10.1016/j.isci.2022.105348
  • 语种:English
  • 出版社:Elsevier
  • 摘要:SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), has infected hundreds of millions of people and caused millions of deaths. Looking for valid druggable targets with minimal side effects for the treatment of COVID-19 remains critical. After discovering host genes from multiscale omics data, we developed an end-to-end network method to investigate drug-host gene(s)-coronavirus (CoV) paths and the mechanism of action between the drug and the host factor in a directional network. We also inspected the potential side effect of the candidate drug on several common comorbidities. We established a catalog of host genes associated with three CoVs. Rule-based prioritization yielded 29 Food and Drug Administration (FDA)-approved drugs via accounting for the effects of drugs on CoVs, comorbidities, and drug-target confidence information. Seven drugs are currently undergoing clinical trials as COVID-19 treatment. This catalog of druggable host genes associated with CoVs and the prioritized repurposed drugs will provide a new sight in therapeutics discovery for severe COVID-19 patients.Graphical abstractDisplay OmittedHighlights•A catalog of host genes associated with three CoVs from multi-omics•Drug repositioning utilized the direction information in the network•Drug prioritization considered the side/beneficial effects on comorbidities•Seven of twenty-nine prioritized approved drugs are in clinical trials for COVID-19Virology; Drugs
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