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.
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)
