Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19
Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19
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双嘧达莫对 COVID-19 重症患者的潜在治疗作用
DOI：
10.1016/j.apsb.2020.04.008
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发表时间：
2020-07-01
影响因子：
14.5
通讯作者：
Luo, Hai-Bin
中科院分区：
文献类型：
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作者：
Liu, Xiaoyan;Li, Zhe;Luo, Hai-Bin
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染可引起急性呼吸窘迫综合征、高凝状态、高血压和多器官功能障碍。目前迫切需要具有安全临床特征的有效抗病毒药物来改善总体预后。在对随机收集的124名COVID-19患者队列的分析中，我们发现D-二聚体浓度升高所指示的高凝状态与疾病严重程度相关。通过对美国FDA批准的药物库的虚拟筛选，我们在计算机上鉴定了一种抗凝剂双嘧达莫（DIP），其在体外抑制SARS-CoV-2复制。在一项涉及31名COVID-19患者的概念验证试验中，与对照患者相比，补充DIP与D-二聚体浓度显著降低（P < 0.05），循环中淋巴细胞和血小板恢复增加以及临床结局显著改善相关。特别是，所有8例接受DIP治疗的重症患者均显示出显著改善：7例患者（87.5%）达到临床治愈并出院，而其余1例患者（12.5%）处于临床缓解状态。(C)2020中国药学会、中国医学科学院药物研究所。制作和主办：Elsevier B. V.
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. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.