First clinical trial of dipyridamole for severely ill patients with COVID-19 shows remarkable benefits.

Key Messages

Virtual screening of a U.S. FDA-approved drug library identified dipyridamole as a strong, potential inhibitor of the SARS-CoV-2 protease Mpro - a critical protein needed for the virus to replicate.

The predicted dose needed to block viral replication falls within the commonly approved dose range of dipyridamole when used to treat hypercoagulability - the tendency of blood to clot.

A controlled clinical trial in several Chinese hospitals studied 31 COVID-19 patients who had pneumonia in both lungs. Twenty of the patients were in severe condition including four who were receiving mechanical ventilation.

Fourteen patients were given 50 mg of dipyridamole by mouth three times a day (total 150 mg) for 14 days in addition to standard therapy. The 17 patients in the control group received only standard therapy.

The death rate observed in patients taking dipyridamole was 7.1% compared to 23.5% in the patients not taking the drug.

In addition, D-dimer, an indicator of blood clotting activity, and other vital blood indexes improved rapidly in the patients taking dipyridamole compared to patients not taking the drug. Viral clearance also occurred 1.6 days faster in the patients taking dipyridamole.

At the end of the trial, 87.5% of severely ill patients who took dipyridamole were discharged compared to 33.3% of severely ill patients who did not take the drug.

Acta Pharmaceutica Sinica B

Publication Date: July 1, 2020
Peer Reviewed: Yes
Publication Type: Original | Clinical Prospective, Preclinical
DOI: https://www.doi.org/10.1016/j.apsb.2020.04.008

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

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

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 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.