The anti COVID-19 performance of seaweed extract is much better than remdesivir

Earlier this year, the news that Gilead’s antiviral drug Remdesivir (Remdesivir) cured American patients with new coronary pneumonia made people have great expectations for this drug. Studies have shown that Remdesivir has not greatly improved the fatality rate of new coronary pneumonia, but it can help patients recover. Recently, researchers have found through cell experiments that a kind of seaweed extract has a much better resistance to the new coronavirus than remdesivir.

The spike protein on the surface of the new coronavirus will attach to the ACE-2 receptor on the surface of human cells. Once fixed, the virus injects its own genetic material into the cell, hijacking the cellular machinery to replicate the virus. But viruses can also be easily deceived. By locking the virus on a "bait molecule" that provides a similar receptor, the neutralized virus will be captured and eventually degraded naturally. Previous studies have shown that this decoy technology can catch viruses such as dengue fever, Zika virus and influenza A.

Recently, some researchers have used this bait technology to test the antiviral efficacy of several polysaccharides against the new coronavirus, and found that one of the edible seaweed extracts has much better performance than remdesivir.

The research was led by Rensselaer Polytechnic University in the United States and was published online on "Cell Discovery" on July 24. The title is "Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro".

This research is the latest example of the decoy strategy developed by researchers at Rensselaer Polytechnic University's Center for Biotechnology and Interdisciplinary Research (CBIS) for new coronaviruses.

The corresponding author of the study, Professor Jonathan Dordick, Department of Chemistry and Biological Engineering, Rensselaer Polytechnic Institute, said: "We are trying to block viral infections in order to quickly respond to epidemics, but the reality is that we do not have powerful antiviral drugs. To protect ourselves To protect against future epidemics, we need a set of methods that can quickly adapt to emerging viruses."

Heparin is a common blood thinner, one of which is a variant of heparin that removes anticoagulant properties, and is comparable to remdesivir in inhibiting SARS-CoV-2 infection of mammalian cells.

This study tested the resistance in three heparin variants (heparin, heparin trisulfate, and a non-anticoagulant low molecular weight heparin) and two fucoidans extracted from seaweed (RPI-27 and RPI-28). Viral activity. These five compounds are all long-chain sulfated polysaccharides of sugar molecules. A combined study published in Antiviral Research earlier this month showed that this structural conformation is an effective bait.

The researchers conducted a dose-response study called EC50 (abbreviated form of the effective concentration of a compound that inhibits 50% of viral infectivity). In the experiment, all five compounds were effective on mammalian cells. For EC50 results given in molar concentrations, the lower the value, the more effective the compound.

The EC50 value of RPI-27 is about 83 nanomolar, while the previous similar independent in vitro test of Radixivir on the same mammalian cell yielded an EC50 value of 770 nanomolar. The EC50 value of heparin is 2.1 micromolar, which is approximately one third of the activity of remdesivir, while the EC50 value of non-anticoagulant heparin analogues is 5.0 micromolar, which is approximately one-fifth of the activity of remdesivir One.

Another test found that even at the highest tested concentration, none of the five compounds were cytotoxic.

Professor Robert Linhardt, Department of Chemistry and Biological Engineering, Rensselaer Polytechnic Institute, said: "This new infection method has aroused our interest. The current idea is that COVID-19 infection starts in the nasal cavity, and any substance in the experiment Both may be the basis of nasal sprays. If the infection can be treated as soon as possible, then there is a way to block the infection." He is working with Professor Dordick to develop a decoy strategy.

Professor Dordick added that seaweed extracts "can be used as the basis for oral preparations to combat potential gastrointestinal infections."

When studying the sequencing data of SARS-CoV-2, Dordick and Linhardt identified several motifs in the structure of the spike protein, which are expected to be compatible with heparin. This result was confirmed in the binding study. Spike protein is wrapped in a large amount of glycans, which is an adaptive response that can protect it from the human body enzymes that may degrade it and allow it to bind to specific receptors on the cell surface.

Dordick said: "This is a very complicated mechanism. Frankly speaking, we don't know all the details, but we are getting more information. This study clearly shows that the larger the molecular weight of sulfate polysaccharides, the molecular traps The greater the number, the more viruses can be caught."

CBIS Director Deepak Vashishth said: "This exciting study by Professor Dordick and Linhardt aims to address the challenge of the COVID-19 pandemic by studying new treatments and the use of existing drugs."