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
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.
