An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19 PMID: 33895786

ADC Targets in Oncology

2026-04-10

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

Signal Transduct Target Ther. 2021 Apr 24;6(1):165. doi: 10.1038/s41392-021-00568-6.

Yiyue Ge ^# ¹ ² , Tingzhong Tian ^# ¹ ² , Suling Huang ^# ³ , Fangping Wan ^# ¹ , Jingxin Li ^# ² , Shuya Li ¹ , Xiaoting Wang ⁴ , Hui Yang ⁴ , Lixiang Hong ¹ , Nian Wu ¹ , Enming Yuan ¹ , Yunan Luo ⁵ , Lili Cheng ⁶ , Chengliang Hu ⁶ , Yipin Lei ⁴ , Hantao Shu ¹ , Xiaolong Feng ⁷ ⁸ , Ziyuan Jiang ⁹ , Yunfu Wu ¹⁰ , Ying Chi ² , Xiling Guo ² , Lunbiao Cui ² , Liang Xiao ¹¹ , Zeng Li ¹¹ , Chunhao Yang ³ , Zehong Miao ³ , Ligong Chen ⁶ ¹² , Haitao Li ¹³ , Hainian Zeng ⁴ , Dan Zhao ¹⁴ , Fengcai Zhu ¹⁵ ¹⁶ , Xiaokun Shen ¹⁷ , Jianyang Zeng ¹⁸

Affiliations

1. Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, China.
2. NHC Key laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Diseases Control and Prevention, Nanjing, Jiangsu Province, China.
3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
4. Silexon AI Technology Co., Ltd., Nanjing, Jiangsu Province, China.
5. Department of Computer Science, University of Illinois at Urbana-Champaign, Illinois, IL, USA.
6. School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
7. School of Electronic Information and Communications, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
8. Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
9. Department of Automation, Tsinghua University, Beijing, China.
10. Inner Mongolia Alashan League Organization Establishment Committee Office Electronic Support Center, Alashan, Inner Mongolia, China.
11. Convalife (Shanghai) Co., Ltd., Shanghai, China.
12. Advanced Innovation Center for Human Brain Protection, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
13. Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
14. Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, China. [email protected].
15. NHC Key laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Diseases Control and Prevention, Nanjing, Jiangsu Province, China. [email protected].
16. Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu Province, China. [email protected].
17. Convalife (Shanghai) Co., Ltd., Shanghai, China. [email protected].
18. Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, China. [email protected].
# Contributed equally.

Abstract

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.