An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19

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 m...

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Autores principales: Ge, Yiyue, Tian, Tingzhong, Huang, Suling, Wan, Fangping, Li, Jingxin, Li, Shuya, Wang, Xiaoting, Yang, Hui, Hong, Lixiang, Wu, Nian, Yuan, Enming, Luo, Yunan, Cheng, Lili, Hu, Chengliang, Lei, Yipin, Shu, Hantao, Feng, Xiaolong, Jiang, Ziyuan, Wu, Yunfu, Chi, Ying, Guo, Xiling, Cui, Lunbiao, Xiao, Liang, Li, Zeng, Yang, Chunhao, Miao, Zehong, Chen, Ligong, Li, Haitao, Zeng, Hainian, Zhao, Dan, Zhu, Fengcai, Shen, Xiaokun, Zeng, Jianyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065335/
https://www.ncbi.nlm.nih.gov/pubmed/33895786
http://dx.doi.org/10.1038/s41392-021-00568-6
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author Ge, Yiyue
Tian, Tingzhong
Huang, Suling
Wan, Fangping
Li, Jingxin
Li, Shuya
Wang, Xiaoting
Yang, Hui
Hong, Lixiang
Wu, Nian
Yuan, Enming
Luo, Yunan
Cheng, Lili
Hu, Chengliang
Lei, Yipin
Shu, Hantao
Feng, Xiaolong
Jiang, Ziyuan
Wu, Yunfu
Chi, Ying
Guo, Xiling
Cui, Lunbiao
Xiao, Liang
Li, Zeng
Yang, Chunhao
Miao, Zehong
Chen, Ligong
Li, Haitao
Zeng, Hainian
Zhao, Dan
Zhu, Fengcai
Shen, Xiaokun
Zeng, Jianyang
author_facet Ge, Yiyue
Tian, Tingzhong
Huang, Suling
Wan, Fangping
Li, Jingxin
Li, Shuya
Wang, Xiaoting
Yang, Hui
Hong, Lixiang
Wu, Nian
Yuan, Enming
Luo, Yunan
Cheng, Lili
Hu, Chengliang
Lei, Yipin
Shu, Hantao
Feng, Xiaolong
Jiang, Ziyuan
Wu, Yunfu
Chi, Ying
Guo, Xiling
Cui, Lunbiao
Xiao, Liang
Li, Zeng
Yang, Chunhao
Miao, Zehong
Chen, Ligong
Li, Haitao
Zeng, Hainian
Zhao, Dan
Zhu, Fengcai
Shen, Xiaokun
Zeng, Jianyang
author_sort Ge, Yiyue
collection PubMed
description 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.
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spelling pubmed-80653352021-04-26 An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19 Ge, Yiyue Tian, Tingzhong Huang, Suling Wan, Fangping Li, Jingxin Li, Shuya Wang, Xiaoting Yang, Hui Hong, Lixiang Wu, Nian Yuan, Enming Luo, Yunan Cheng, Lili Hu, Chengliang Lei, Yipin Shu, Hantao Feng, Xiaolong Jiang, Ziyuan Wu, Yunfu Chi, Ying Guo, Xiling Cui, Lunbiao Xiao, Liang Li, Zeng Yang, Chunhao Miao, Zehong Chen, Ligong Li, Haitao Zeng, Hainian Zhao, Dan Zhu, Fengcai Shen, Xiaokun Zeng, Jianyang Signal Transduct Target Ther Article 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. Nature Publishing Group UK 2021-04-24 /pmc/articles/PMC8065335/ /pubmed/33895786 http://dx.doi.org/10.1038/s41392-021-00568-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ge, Yiyue
Tian, Tingzhong
Huang, Suling
Wan, Fangping
Li, Jingxin
Li, Shuya
Wang, Xiaoting
Yang, Hui
Hong, Lixiang
Wu, Nian
Yuan, Enming
Luo, Yunan
Cheng, Lili
Hu, Chengliang
Lei, Yipin
Shu, Hantao
Feng, Xiaolong
Jiang, Ziyuan
Wu, Yunfu
Chi, Ying
Guo, Xiling
Cui, Lunbiao
Xiao, Liang
Li, Zeng
Yang, Chunhao
Miao, Zehong
Chen, Ligong
Li, Haitao
Zeng, Hainian
Zhao, Dan
Zhu, Fengcai
Shen, Xiaokun
Zeng, Jianyang
An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
title An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
title_full An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
title_fullStr An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
title_full_unstemmed An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
title_short An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19
title_sort integrative drug repositioning framework discovered a potential therapeutic agent targeting covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065335/
https://www.ncbi.nlm.nih.gov/pubmed/33895786
http://dx.doi.org/10.1038/s41392-021-00568-6
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