Molecules from Seaweed Show Antiviral Properties Against SARS-CoV-2

Research Overview

Recent studies have demonstrated that two molecules derived from edible seaweeds exhibit antiviral activity against SARS-CoV-2, the virus responsible for COVID-19. A team of scientists from Rensselaer Polytechnic Institute in the USA previously established that heparin, an anticoagulant, binds effectively to the spike protein on the SARS-CoV-2 virus. Building on this foundation, the researchers investigated the antiviral properties of heparin and related compounds in cells infected with SARS-CoV-2.

Findings on Antiviral Efficacy

The investigation revealed that two specific seaweed-derived molecules—RPI-27 and RPI-28—were able to inhibit viral infection at significantly lower concentrations than remdesivir, a drug currently used to treat COVID-19. Heparin also demonstrated enhanced antiviral activity compared to remdesivir. The study assessed the EC50 values, which indicate the effective concentration needed to inhibit 50% of viral infectivity, for five compounds on infected mammalian cells. All five compounds, including heparin, are classified as long chains of sugar molecules known as sulfated polysaccharides. Among these, RPI-27, RPI-28, and heparin showed EC50 values considerably lower than those reported for remdesivir, indicating their effectiveness at lower concentrations. Notably, none of the tested molecules exhibited toxic effects on cells, even at the highest concentrations.

Mechanism of Action

RPI-27 and RPI-28 are characterized as ‘highly branched’ polysaccharides, which may account for their superior ability to inhibit the virus by binding to the spike protein of the viral particle. By functioning as a ‘decoy,’ these polysaccharides could hinder the viral particle’s attachment to human cells, thus reducing its infectivity. Molecular modeling supports this theory, revealing multiple binding sites for sulfated polysaccharides like heparin on the spike protein of SARS-CoV-2. While the exact interaction mechanism between these polysaccharides and the viral particle remains unclear, Dr. Dordick, the lead researcher, noted, “It’s a very complicated mechanism… One thing that’s become clear with this study is that the larger the molecule, the better the fit. The more successful compounds are the larger sulfated polysaccharides that offer a greater number of sites on the molecules to trap the virus.”

Potential for Clinical Application

Given the high potency and low toxicity of these natural antiviral agents, the researchers propose that these molecules be tested in combination with existing therapies on human cell cultures and eventually in clinical trials. Possible administration methods include nasal sprays, metered dose inhalers (similar to those used for asthma), or oral delivery. These options would offer a simpler alternative to the intravenous administration currently required for remdesivir. Dr. Linhardt, a collaborator on the study, emphasized, “The current thinking is that the COVID-19 infection starts in the nose and either of these substances could be the basis for a nasal spray. If you could simply treat the infection early, or even treat before you have the infection, you would have a way of blocking it before it enters the body.”

Implications for Future Pandemics

The ‘decoy’ strategy utilized to trap the virus has proven effective against other viruses, such as dengue and Zika, suggesting that these natural antiviral molecules could play a significant role in combating both current and future pandemics.

References

Kwon, P.S., Oh, H., Kwon, S. et al. Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro. Cell Discov 6, 50 (2020). https://doi.org/10.1038/s41421-020-00192-8

Image by Gerd Altmann from Pixabay