Over a hundred potential vaccines and drugs are being researched for the prevention and treatment of the novel coronavirus. Remdesivir, the first drug known to be effective against SARS-CoV-2, brought a lot of hope to everyone when it received approval for treatment.
However, the scientific community is still working on finding more effective ways to deal with the disease. Various studies are being conducted all over the globe to find out more easily-available and cheaper medications for the infection.
In this process, heparin (an anticoagulant) was also found to be effective in controlling blood clotting and arrhythmias in COVID-19 patients. The drug is being tested in the UK ACCORD trials for its effectiveness against the coronavirus infection.
Now, a study published in the journal Cell Discovery has suggested that seaweed extract may be more effective than remdesivir or heparin in neutralising the COVID-19 causing virus, SARS-CoV-2.
The SARS-COV-2 virus binds to the ACE2 receptors on the surface of healthy cells to gain entry into these cells. However, a study published in the journal Antiviral Research, indicated that the virus may also have specific binding sites on its spike protein for glycosaminoglycans (a type of polysaccharide sugar) on the cell surface. It is with these sites that heparin can bind strongly to and prevent the entry of the virus inside healthy cells.
Since heparin is a linear polysaccharide, the current study aimed at testing the binding efficiency of heparin and its closely related polysaccharides with the COVID-19 causing virus.
Five different polysaccharides were taken for the study. These included:
- Various variants of heparin: heparin, trisulfate heparin, non-coagulant low molecular weight heparin
- Two fucoidans, RPI-27 and RPI-28 from the seaweed Saccharina japonica, commonly called sweet kelp. Both RPI-27 and RPI-28 are branched polysaccharides with a more complex structure than heparin.
- Polysaccharides like heparan sulfate, chondroitin sulfate and keratan sulfate were also included in the study.
All the polysaccharides were exposed to the virus to see how they bind. For a control, the S protein of the virus was taken without a polysaccharide.
To quantify the effects of each compound, the scientists used something called an EC50 study, which studied the amount of a particular compound needed to neutralise 50 percent of the virus. So, the less the amount needed, the more potent the compound will be.
Here is what was found:
- RPI-27 was the most potent compound, with an EC50 of about 83nM (nanomolar). RPI-28 had a lower EC50 than RPI-27 due to its low molecular weight: it was 1.2 µM (micromolar). Micro is equal to 1/106 and nano is equal to 1/109.
- The EC50 of heparin was 2.1 µM and that of trisulfate heparin was 5 µM.
- Low molecular weight heparin had an EC50 of 55 µM.
- The other polysaccharides like heparan sulfate, chondroitin sulfate and keratan sulfate could not compete with heparin to bind with the SARS-COV-2 receptors and hence they were taken out of the study.
- None of the compounds had any toxic effects on healthy cells
In previous studies, the EC50 of remdesivir was found to be around 770nM and 11.4 µM.
The study suggested that due to their complex and branched structure, the seaweed fucoidans give more binding sites to the coronavirus than the straight-chain heparin, which may be one of the reasons for its low EC50.
“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,” said Jonathan Dordick, the lead researcher of the study in a news release.
The study suggested that all of these compounds can be used as nasal sprays, inhalers or oral doses to control coronavirus infection. This is a much easier way for drug delivery than the more technical intravenous way remdesivir is administered.