期刊
ACTA PHARMACEUTICA SINICA B
卷 10, 期 7, 页码 1205-1215出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2020.04.008
关键词
Dipyridamole; SARS-CoV-2; COVID-19; Treatment; D-dimer; Severe cases
资金
- National Key R&D Program of China [2017YFB0202600, 2020YFC0841400]
- National Natural Science Foundation of China [91742109, 8152204, 31770978, 81773674, 21877134]
- National Health & Medical Research of Australia [1080321, 1143976, 1150425]
- Science Foundation of Guangzhou City (China) [201904020023]
- Guangdong Provincial Key Laboratory of Construction Foundation (China) [2017B030314030]
- Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (China) [2017BT01Y093]
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.
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