Volume 6 Issue 5, May 2021:

Article

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

Yiyue Ge  ORCID: orcid.org/0000-0002-4839-5334,Tingzhong Tian  ORCID: orcid.org/0000-0003-4899-0632,Suling Huang,Fangping Wan,Jingxin Li,Shuya Li,Xiaoting Wang,Hui Yang,Lixiang Hong,Nian Wu,Enming Yuan,Yunan Luo,Lili Cheng,Chengliang Hu,Yipin Lei,Hantao Shu,Xiaolong Feng,Ziyuan Jiang,Yunfu Wu,Ying Chi,Xiling Guo,Lunbiao Cui,Liang Xiao,Zeng Li,Chunhao Yang,Zehong Miao  ORCID: orcid.org/0000-0002-0833-6583,Ligong Chen  ORCID: orcid.org/0000-0002-7893-7173,Haitao Li  ORCID: orcid.org/0000-0002-6686-1677,Hainian Zeng,Dan Zhao  ORCID: orcid.org/0000-0003-0195-6031,Fengcai Zhu,Xiaokun Shen &…Jianyang Zeng  ORCID: orcid.org/0000-0003-0950-7716 

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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