Can seaweed really help us fight COVID-19?
Do we already have the powerful drugs we need to treat COVID-19? Maybe. In order to find out, we will also need a clearer perspective and fuller understanding of the drug repurposing process.
As the SARS-CoV-2 virus, which causes COVID-19, traverses the globe, already responsible for more than 18 million infections and more than 700,000 reported deaths worldwide, the public has developed an acute, albeit tragic, understanding that infectious disease cannot be tamed on-demand. Many are understandably focused on the development of a vaccine, and very promising advances in antibody therapeutics are being reported. But we must also recognize that, prior to that breakthrough, medicine is not completely powerless in the battle against this disease.
In the nearer term, attention must be paid to the rapid and creative identification of new and old drugs — and other substances — that have begun to reduce the mortality and morbidity of COVID-19. At Rensselaer Polytechnic Institute, where I currently teach and manage a large research group, for example, we recently found that a common anticoagulant, heparin, shows promise in neutralizing the virus. Additionally, a fucoidan isolated from a brown algae seaweed — in particular, one of the most common species in Japan, Korea, and China — may inhibit viral infectivity approximately eight times more effectively than remdesivir, the current standard-bearer antiviral.
How we came to test the efficacy of seaweed extracts as a potential COVID-19 therapeutic — and where the findings may lead us — serves as an informative example of the approaches that are helping us discover effective new uses for existing substances that may significantly mitigate the threat of this novel disease.
Given the lengthy drug approval process, repurposing existing drugs or later-stage drug candidates represents the quickest path to the patient, as these substances have gone through all or most stages of the approval process of the U.S. Food and Drug Administration. Of course, not just any repurposed drug will do.
Remdesivir itself is an example of a repurposed drug candidate, having made it into Phase 3 human clinical trials in the U.S. for treatment of Ebola. The drug has seen modest success as an antiviral in seriously ill COVID-19 patients, with a reduction in length of hospital stays. Another repurposed drug for COVID-19 treatment, one that seems clearly effective in late-stage patients, is the corticosteroid dexamethasone. This decades-old, widely used, anti-inflammatory, immunosuppressant resulted in a roughly 30 percent reduction in mortality among ventilated patients.
We joined the fight against COVID-19 by turning our attention to the mechanism of viral entry into target cells. We knew that spike proteins that protrude from the surface of viruses like SARS-CoV-2 initially bind to their target cells through cell-surface polysaccharides. These long sugar-like chains are critical to human cell function and they also possess diverse therapeutic applications. One related molecule is heparin, a common anticoagulant used in kidney dialysis, cardiac surgeries and deep vein thrombosis treatment. Importantly, heparin is chemically and structurally similar to the cell surface polysaccharides.
A 100-year-old drug, heparin has already proven to be a key drug for the treatment of blood clots that form in severely ill COVID-19 patients. During the height of the pandemic in New York City, researchers at Rensselaer and the Icahn School of Medicine at Mount Sinai posited that use of a potent anticoagulant therapy may be indicated. As a result, severely ill patients were given heparin, and the mortality of patients on ventilators was cut in half.
Additionally, because heparin appears to mimic the properties of cell surface polysaccharides, we proposed that the drug could serve as a decoy. It could bind to the virus before the virus was able to bind to the cell surface, rendering SARS-CoV-2 unable to infect its target. In fact, we found that heparin bound exceptionally tightly to the virus spike protein.
In a follow-up cell-based study, we demonstrated that — unrelated to its well-known, FDA-approved use — heparin could indeed prevent infection of target cells. It proved to be a potent inhibitor of the ability of SARS-CoV-2 to bind to and infect mammalian cells, a necessary requirement for a potential therapeutic. Variants of heparin also inhibited viral infectivity, including a non-anticoagulant biosynthetic heparin precursor. We decided to also test other natural polysaccharides with a similar structure, which is how we discovered the potency of certain seaweed extracts.
Repurposing can lead to new ways of delivering existing drugs or combinations of drugs to treat a disease. For example, with respect to delivery, the extraordinarily strong binding of heparin to SARS-CoV-2 could be used to neutralize the virus in easy-to-reach places. Since COVID-19 is known to start in the upper airways, including the nasal passage, it may be possible to consider a heparin-based nasal spray. Heparin is safe and would not likely result in bleeding if delivered intranasally. Seaweed polysaccharides would also likely be safe taken intranasally, and could very likely be delivered orally to address potential gastrointestinal infection.
In just six months, COVID-19 has yielded unique collaborations of clinicians, scientists and engineers to develop better treatment modalities and identify old and new drugs that may reduce morbidity and mortality. This is a wakeup call to the oldest scourge of mankind — infectious disease. We need both basic research to understand viruses and other pathogens, and translational research to advance new therapies quickly, efficiently and safely to the clinic and then to patients. This is expensive, but extremely cost-effective when this knowledge base can guide us through the COVID-19 pandemic and position ourselves for the inevitable next pandemic.
Jonathan S. Dordick, Ph.D. is the Howard P. Isermann professor of Chemical and Biological Engineering, and Biological Sciences at Rensselaer Polytechnic Institute, where he previously served as vice president for research. He has made foundational contributions in biomolecular discovery and engineering related to infectious diseases (including COVID-19) and biomanufacturing, has published nearly 400 papers, is an inventor on nearly 50 patents, and has founded five biotechnology companies.
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