文章基本信息

标题：Rational drug repositioning for coronavirus-associated diseases using directional mapping and side-effect inference
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作者：Jianhua Wang ; Jiaojiao Liu ; Menghan Luo 等
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