An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
文献类型：期刊论文
| 作者 | Ge, Yiyue2,3; Tian, Tingzhong2,3; Huang, Suling4 ; Wan, Fangping2; Li, Jingxin3; Li, Shuya2; Wang, Xiaoting5; Yang, Hui5; Hong, Lixiang2; Wu, Nian2
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| 刊名 | SIGNAL TRANSDUCTION AND TARGETED THERAPY
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| 出版日期 | 2021-04-24 |
| 卷号 | 6期号:1页码:16 |
| ISSN号 | 2095-9907 |
| DOI | 10.1038/s41392-021-00568-6 |
| 通讯作者 | Zhao, Dan(zhaodan2018@tsinghua.edu.cn) ; Zhu, Fengcai(jszfc@vip.sina.com) ; Shen, Xiaokun(steve.shen@convalife.com) ; Zeng, Jianyang(zengjy321@tsinghua.edu.cn) |
| 英文摘要 | The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection. |
| WOS关键词 | RESPIRATORY SYNDROME-CORONAVIRUS ; POLY(ADP-RIBOSE) POLYMERASE PARP ; NF-KAPPA-B ; STRUCTURAL BASIS ; IN-VITRO ; NUCLEOCAPSID PROTEIN ; CYTOKINE STORM ; INHIBITORS ; INFECTION ; PJ34 |
| 资助项目 | National Natural Science Foundation of China[61872216] ; National Natural Science Foundation of China[81630103] ; National Natural Science Foundation of China[31900862] ; National Natural Science Foundation of China[31725014] ; Jiangsu Provincial Emergency Project on Prevention and Control of COVID-19 Epidemic[BE2020601] ; Nation Science and Technology Major Projects for Major New Drugs Innovation and Development[2018ZX09711003-004-002] ; Nation Science and Technology Major Projects for Major New Drugs Innovation and Development[2019ZX09301010] ; Pudong New Area Science and Technology Development Foundation[PKX2019-S08] ; Turing AI Institute of Nanjing ; Zhongguancun Haihua Institute for Frontier Information Technology |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000733242600003 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300797]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhao, Dan; Zhu, Fengcai; Shen, Xiaokun; Zeng, Jianyang |
| 作者单位 | 1.Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Med, Dept Basic Med Sci, Beijing, Peoples R China 2.Tsinghua Univ, Inst Interdisciplinary Informat Sci, Beijing, Peoples R China 3.Jiangsu Prov Ctr Dis Control & Prevent, NHC Key Lab Enter Pathogen Microbiol, Nanjing, Jiangsu, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 5.Silexon Technol Co Ltd, Nanjing, Jiangsu, Peoples R China 6.Univ Illinois, Dept Comp Sci, Urbana, IL USA 7.Tsinghua Univ, Sch Pharmaceut Sci, Beijing, Peoples R China 8.Huazhong Univ Sci & Technol, Sch Elect Informat & Communicat, Wuhan, Hubei, Peoples R China 9.Huazhong Univ Sci & Technol, Inst Pathol, Tongji Hosp, Tongji Med Coll, Wuhan, Hubei, Peoples R China 10.Tsinghua Univ, Dept Automat, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ge, Yiyue,Tian, Tingzhong,Huang, Suling,et al. An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2021,6(1):16. |
| APA | Ge, Yiyue.,Tian, Tingzhong.,Huang, Suling.,Wan, Fangping.,Li, Jingxin.,...&Zeng, Jianyang.(2021).An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19.SIGNAL TRANSDUCTION AND TARGETED THERAPY,6(1),16. |
| MLA | Ge, Yiyue,et al."An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19".SIGNAL TRANSDUCTION AND TARGETED THERAPY 6.1(2021):16. |
入库方式： OAI收割
来源：上海药物研究所
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