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

Liu, Xiaoyan; Li, Zhe; Liu, Shuai; Sun, Jing; Chen, Zhanghua; Jiang, Min; Zhang, Qingling; Wei, Yinghua; Wang, Xin; Huang, Yi-You; Shi, Yinyi; Xu, Yanhui; Xian, Huifang; Bai, Fan; Ou, Changxing; Xiong, Bei; Lew, Andrew M.; Cui, Jun; Fang, Rongli; Huang, Hui; Zhao, Jincun; Hong, Xuechuan; Zhang, Yuxia; Zhou, Fuling; Luo, Hai-Bin

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 Corona Virus Disease 2019 (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. Food and Drug Administration (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.