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

ORIGINAL ARTICLE
Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19
Author links open overlay panelXiaoyanLiua†ZheLib†ShuaiLiuac†JingSund†ZhanghuaChenef†MinJiangg†QinglingZhangd†YinghuaWeigXinWanghYi-YouHuangbYinyiShicYanhuiXueHuifangXianeFanBaifChangxingOudBeiXiongaAndrew M.LewiJunCuij…Hai-BinLuob
https://doi.org/10.1016/j.apsb.2020.04.008Get rights and content
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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.

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Dipyridamole bound to the SARS-CoV-2 protease Mpro after identified via the virtual screening and bioassay validation, and thus suppressed viral replication in vitro. As a result, dipyridamole supplementation was associated with significantly decreased concentrations of D-dimers, increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients.