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

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IMAGE: 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... view more 

Credit: Acta Pharmaceutica Sinica B

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. In recent months, SARS-CoV-2 has gradually spread to more than 200 countries and regions, resulting in more than 500,000 deaths globally.

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, the authors 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, the authors 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 for the severely ill patients in comparison to the control patients. In summary, DIP could be used for the treatment of severely ill patients with COVID-19 through antiviral and anticoagulation effects.

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Author Biographies

Hai-Bin Luo, Deputy Dean, School of Pharmacy, Sun Yat-sen University, Guangzhou, China. Research interests: new drug design methods and new drug development for inflammatory diseases of the lungs.

Fuling Zhou, Director, Department of Hematology, Wuhan University Central South Hospital, Wuhan University School of Medicine, Wuhan, China. Research interests: leukaemia and other blood disorders.

Yuxia Zhang, Guangzhou Women and Children Medical Center, Guangzhou Medical University, Guangzhou, China. Research interests: regional immune mechanisms of infection (pneumonia) and chronic disease.

Xuechuan Hong, Professor, School of Pharmacy, Wuhan University, Wuhan, China. Research interests: new drug development.

Jincun Zhao, Director, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China. Research interests: research on the pathogenic mechanism and related prevention and treatment methods of human new sudden respiratory infectious diseases.

Article reference: Xiaoyan Liu, Zhe Li, Shuai Liu, Jing Sun, Zhanghua Chen, Min Jiang, Qingling Zhang, Yinghua Wei, Xin Wang, Yi-You Huang, Yinyi Shi, Yanhui Xu, Huifang Xian, Fan Bai, Changxing Ou, Bei Xiong, Andrew M. Lew, Jun Cui, Rongli Fang, Hui Huang, Jincun Zhao, Xuechuan Hong, Yuxia Zhang, Fuling Zhou, Hai-Bin Luo, Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19, Acta Pharmaceutica Sinica B, 2020, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2020.04.008

Keywords: Dipyridamole; SARS-CoV-2; COVID-19; Treatment; D-dimer; Severe cases

The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association. Acta Pharmaceutica Sinica B (APSB) is a bimonthly journal, in English, which publishes significant original research articles, rapid communications and high quality reviews of recent advances in all areas of pharmaceutical sciences -- including pharmacology, pharmaceutics, medicinal chemistry, natural products, pharmacognosy, pharmaceutical analysis and pharmacokinetics.

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CiteScore: 10.5

Impact Factor: 7.097

5-Year Impact Factor: 7.865

Source Normalized Impact per Paper (SNIP): 2.210

SCImago Journal Rank (SJR): 1.792

ISSN 2211-3835

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