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.