Acta Pharmaceutica Sinica B (Jul 2020)
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,
- Jincun Zhao,
- Xuechuan Hong,
- Yuxia Zhang,
- Fuling Zhou,
- Hai-Bin Luo
Affiliations
- Xiaoyan Liu
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Zhe Li
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
- Shuai Liu
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Dawu County People's Hospital, Xiaogan 432826, China
- Jing Sun
- State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
- Zhanghua Chen
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510623, China; Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China
- Min Jiang
- Department of Infectious Disease and Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
- Qingling Zhang
- State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
- Yinghua Wei
- Department of Infectious Disease and Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
- Xin Wang
- Center for Innovative Marine Drug Screening & Evaluation (QNLM), School of Medicine and Pharmacy, Ocean University of China, Qingdao 266100, China
- Yi-You Huang
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
- Yinyi Shi
- Dawu County People's Hospital, Xiaogan 432826, China
- Yanhui Xu
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510623, China
- Huifang Xian
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510623, China
- Fan Bai
- Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China
- Changxing Ou
- State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China
- Bei Xiong
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Andrew M. Lew
- Walter and Eliza Hall Institute of Medical Research and Department of Microbiology & Immunology, University of Melbourne, Parkville, Vic 3052, Australia
- Jun Cui
- School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China
- Rongli Fang
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510623, China
- Hui Huang
- Cardiovascular Department, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518000, China
- Jincun Zhao
- State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; Corresponding authors.
- Xuechuan Hong
- State Key Laboratory of Virology, College of Science, Innovation Center for Traditional Tibetan Medicine Modernization and Quality Control, Medical College, Tibet University, Lhasa 850000, China; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China; Corresponding authors.
- Yuxia Zhang
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou 510623, China; Corresponding authors.
- Fuling Zhou
- Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Corresponding authors.
- Hai-Bin Luo
- Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Corresponding authors.
- Journal volume & issue
-
Vol. 10,
no. 7
pp. 1205 – 1215
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 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.
