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

作　　者：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 

机构地区：[1]Department of Hematology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China [2]Guangdong Provincial Key Laboratory of New Drug Design and Evaluation,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China [3]Dawu County People’s Hospital,Xiaogan 432826,China [4]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 [5]Guangzhou Institute of Pediatrics,Guangzhou Women and Children’s Medical Center,State Key Laboratory of Respiratory Diseases,Guangzhou Medical University,Guangzhou 510623,China [6]Biomedical Pioneering Innovation Center(BIOPIC),School of Life Sciences,Peking University,Beijing 100871,China [7]Department of Infectious Disease and Department of Pediatrics,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China [8]Center for Innovative Marine Drug Screening&Evaluation(QNLM),School of Medicine and Pharmacy,Ocean University of China,Qingdao 266100,China [9]Walter and Eliza Hall Institute of Medical Research and Department of Microbiology&Immunology,University of Melbourne,Parkville,Vic 3052,Australia [10]School of Life Sciences,Sun Yat-sen University,Guangzhou 510006,China [11]Cardiovascular Department,The Eighth Affiliated Hospital,Sun Yat-sen University,Shenzhen 518000,China [12]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 [13]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

出　　处：《Acta Pharmaceutica Sinica B》2020年第7期1205-1215,共11页药学学报（英文版）

基　　金：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.;Beijing Taikang Yicai Foundation(Beijing,China)

摘　　要：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.

关 键 词：DIPYRIDAMOLE SARS-CoV-2 COVID-19 TREATMENT D-DIMER Severe cases 

分 类 号：R563.1[医药卫生—呼吸系统]