Study Shows Heparin May Neutralize the Virus That Causes COVID-19

Recent research has demonstrated that occurrences of coronavirus disease 2019 (COVID-19) are associated with a significant risk of thrombotic complications. Such complications can range from microvascular thrombosis to venous thromboembolic disease and stroke. These complications have been found to be signs of severe COVID-19 and have been associated with multiorgan failure and an increased risk of mortality.¹

Since thrombotic complications are central determinants of the high mortality rate from COVID-19, researchers have been investigating strategies to prevent thrombosis in patients with the virus. For this reason, certain antithrombotic drugs have been proposed as potential therapies to prevent thrombosis, including treatments such as heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole.¹

Specifically, researchers at the Rensselaer Polytechnic Institute (RPI) recently published a study in Antiviral Research on the use of the FDA-approved anticoagulant heparin in patients with COVID-19. The results demonstrated that heparin may be able to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.²

The researchers at the RPI explained that they investigated heparin as a treatment for patients with COVID-19 because they thought the drug could intercept the spike protein-heparan sulfate interaction through a decoy approach.²

“That’s very similar to how neutralizing antibodies function, where the antibodies bind to the spike protein and prevents that protein from interacting with the ACE2 receptor. We thought that for this to be demonstrable, we had to show that it binds to the spike protein and show how well it binds,” said study co-author Jonathan S. Dordick, PhD, Howard P. Isermann professor of chemical and biological engineering at RPI, in an interview with Healio.²

Dordick explained that the results from the study showed quantitatively that heparin bound tightly to the spike protein. Following this, the researchers created some modeling studies to assess where the treatment bound on the spike protein. Dordick noted that although the study published in Antiviral Research does not detail the activity of neutralizing the virus, his research team published follow-up work in Cell Discovery that demonstrates that heparin does inhibit SARS-CoV-2 from infecting cells.²

“Heparin is a large polysaccharide, so it will wrap itself around the spike protein. Once it does that, the virus ultimately disintegrates; if a virus can’t infect a cell, it doesn’t have a very long lifetime,” Dordick said in the interview with Healio.²

Due to heparin being derived from an animal source and the associated potential for shortages and other complications, Dordick’s team is currently developing a nonanimal sourced form of heparin as a biosynthetic, with some promising results to date.²

“Some of the nonanticoagulant intermediates leading up to our biosynthetic heparin that showed activity that was nearly the same as natural heparin. That told us the larger size and the degree of sulfation on the heparin play a major role in binding to the spike protein. What makes this even more exciting is that heparin is extremely safe. Physicians have known how to use it for a long time, and they know how to use it quite well,” Dordick told Healio.²

Due to prior shortages of heparin, Dordick explained that his research team is investigating the use of the treatment in an inhalation version or a nasal spray. Specifically, heparin in the form of a nasal spray may be most advantageous, according to Dordick, as the amount needed for a single dose would be so small that it would not significantly deplete the supply of the treatment from its regular and necessary use in surgeries.²

“This is one of several examples of work underway showing that existing drugs can play a major role in treating and preventing the spread of the coronavirus. I would imagine many other viruses would be subject to something similar,” Dordick told Healio. “In fact, the reason we have heparin in our intestines and other organs is likely for anti-infective purposes. It’s not an anticoagulant in our bodies but may be as effective as an antiparasitic. For example, if you think about it in this way, heparin already has the natural function of preventing infection.”²

REFERENCES

• McFadyen JD, Stevens H, Peter K. The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications. Circulation Research. 2020;127:571—587. doi: 10.1161/CIRCRESAHA.120.317447.
• Byrne J. Heparin may neutralize virus that causes COVID-19. Healio. August 28, 2020. healio.com/news/hematology-oncology/20200827/heparin-may-neutralize-virus-that-causes-covid19. Accessed September 10, 2020.