Journal article

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

Xiaoyan Liu, Zhe Li, Shuai Liu, Jing Sun, Zhanghua Chen, Min Jiang, Qingling Zhang, Yinghua Wei, Xin Wang, Yi-You Huang, Yinyi Shi, Yanhui Xu, Huifang Xian, Fan Bai, Changxing Ou, Bei Xiong, Andrew M Lew, Jun Cui, Rongli Fang, Hui Huang Show all

Acta Pharmaceutica Sinica B | INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES | Published : 2020

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 ..

View full abstract

University of Melbourne Researchers

Grants

Awarded by National Key R&D Program of China


Awarded by National Natural Science Foundation of China


Awarded by National Health & Medical Research of Australia


Awarded by Science Foundation of Guangzhou City (China)


Awarded by Guangdong Provincial Key Laboratory of Construction Foundation (China)


Awarded by Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (China)


Funding Acknowledgements

We cordially acknowledge Tencent Cloud and National Supercomputing centers in Guangzhou, Shenzhen, and Tianjin, China for providing HPC resources for virtual screening and free energy perturbation calculations, and Prof. H. Ke at the University of North Carolina, Chapel Hill, NC, USA for comments. We cordially acknowledge National Key R&D Program of China (2017YFB0202600 and 2020YFC0841400), National Natural Science Foundation of China (91742109, 8152204, 31770978, 81773674, and 21877134), National Health & Medical Research of Australia (1080321, 1143976 and 1150425), Science Foundation of Guangzhou City (201904020023, China), Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme (2016 and 2019, China), Guangdong Provincial Key Laboratory of Construction Foundation (2017B030314030, China), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01Y093, China), Zhejiang University special scientific research fund for COVID-19 prevention and control (China), National Health & Medical Research of Australia (1080321, 1143976, and 1150425), Taikang Insurance Group Co., Ltd. and Beijing Taikang Yicai Foundation (Beijing, China), and philanthropy donation from individuals. The funders had no roles in the design and execution of the study.