Rational drug repositioning for coronavirus-associated diseases using directional mapping and side-effect inference

Jianhua Wang; Jiaojiao Liu; Menghan Luo; Hui Cui; Wenwen Zhang; Ke Zhao; Hongji Dai; Fangfang Song; Kexin Chen; Ying Yu; Dongming Zhou; Mulin Jun Li; Hongxi Yang

iScience (Nov 2022)

Rational drug repositioning for coronavirus-associated diseases using directional mapping and side-effect inference

Jianhua Wang,
Jiaojiao Liu,
Menghan Luo,
Hui Cui,
Wenwen Zhang,
Ke Zhao,
Hongji Dai,
Fangfang Song,
Kexin Chen,
Ying Yu,
Dongming Zhou,
Mulin Jun Li,
Hongxi Yang

Affiliations

Jianhua Wang: Department of Epidemiology and Biostatistics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China; Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Jiaojiao Liu: Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Menghan Luo: Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Hui Cui: School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Wenwen Zhang: Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Ke Zhao: Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Hongji Dai: Department of Epidemiology and Biostatistics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
Fangfang Song: Department of Epidemiology and Biostatistics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
Kexin Chen: Department of Epidemiology and Biostatistics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
Ying Yu: Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
Dongming Zhou: Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Corresponding author
Mulin Jun Li: Department of Epidemiology and Biostatistics, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory of Molecular Cancer Epidemiology, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China; Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Corresponding author
Hongxi Yang: Department of Bioinformatics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Corresponding author

Journal volume & issue: Vol. 25, no. 11
p. 105348

Abstract

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Summary: Severe 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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