Blood-clot promoting antiphospholipid antibodies play a role in COVID-19, and can be reduced by dipyridamole.

Key Messages

This study reports a virtual screening approach using a computer modeling method to identify drug candidates as inhibitors of the SARS-CoV-2 main protease, called Mpro.

Out of 25 drugs predicted to inhibit Mpro, 15 were confirmed as strong potential Mpro inhibitors. The most potent potential inhibitor was dipyridamole, which has already demonstrated promising results when used to treat COVID-19 patients in clinical studies.

Blood samples from 172 patients hospitalized for COVID-19 were tested for the presence of antiphospholipid antibodies, which play a major role in blood clot formation. Antiphospholipid antibodies were identified in 52% of the blood samples, thus providing an explanation for the hyper-clotting activity seen in COVID-19.

The same authors have previously demonstrated that dipyridamole reduces the formation of neutrophil extracellular traps (NETs), which are fiber networks involved in blood clotting that increase in response to antiphospholipid antibodies.

Dipyridamole is therefore well positioned to treat COVID-19.

medRxiv

Publication Date: September 15, 2020
Peer Reviewed: No
Publication Type: Original | Preclinical
DOI: https://www.doi.org/10.1101/2020.06.15.20131607

Prothrombotic antiphospholipid antibodies in COVID-19

Yu Zuo, Shanea K. Estes, Ramadan A. Ali, Alex A. Gandhi, Srilakshmi Yalavarthi, Hui Shi, Gautam Sule, Kelsey Gockman, Jacqueline A. Madison, Melanie Zuo, Vinita Yadav, Jintao Wang, Wrenn Woodward, Sean P. Lezak, Njira L. Lugogo, Stephanie A. Smith, James H. Morrissey, Yogendra Kanthi, Jason S. Knight