Source: COVID-19 Drugs  Jul 25, 2020  2 years ago
BREAKING! COVID-19 Drugs: Study Shows That Fucoidan Extracted From Seaweed Outperforms Remdesivir In Inhibiting SARS-CoV-2 In Cell Studies
BREAKING! COVID-19 Drugs: Study Shows That Fucoidan Extracted From Seaweed Outperforms Remdesivir In Inhibiting SARS-CoV-2 In Cell Studies
Source: COVID-19 Drugs  Jul 25, 2020  2 years ago
COVID-19 Drugs: Researchers from Rensselaer Polytechnic Institute-New York, Korea Research Institute of Bioscience and Biotechnology, and Zhejiang University of Technology-China in study involving the test of antiviral effectiveness against the virus that causes COVID-19, found that an extract from edible seaweeds called fucoidan substantially outperformed remdesivir, the current standard antiviral used to combat the disease.

The same study also found that Heparin, a common blood thinner, and a heparin variant stripped of its anticoagulant properties, performed on par with remdesivir in inhibiting SARS-CoV-2 infection in mammalian cells.
The research findings were published in the journal: Cell Discovery.
The SARS-CoV-2 spike protein on the surface of SARS-CoV-2 latches onto the ACE-2 receptor, a molecule on the surface of human cells. Once secured, the virus inserts its own genetic material into the cell, hijacking the cellular machinery to produce replica viruses. But the virus could just as easily be persuaded to lock onto a decoy molecule that offers a similar fit. The neutralized virus would be trapped and eventually degrade naturally.
Previous research has shown this decoy technique works in trapping other viruses, including dengue, Zika, and influenza A.
Dr Jonathan Dordick, lead researcher and a professor of chemical and biological engineering at Rensselaer Polytechnic Institute, “We are learning how to block viral infection, and that is knowledge we are going to need if we want to rapidly confront pandemics. The reality is that we don't have great antivirals. To protect ourselves against future pandemics, we are going to need an arsenal of approaches that we can quickly adapt to emerging viruses."
The study team tested antiviral activity in three variants of heparin (heparin, trisulfated heparin, and a non-anticoagulant low molecular weight heparin) and two fucoidans (RPI-27 and RPI-28) extracted from seaweed. All five compounds are long chains of sugar molecules known as sulfated polysaccharides, a structural conformation that the results of a binding study published earlier this month in Antiviral Research suggested as an effective decoy.
The study team performed a dose response study known as an EC50 -- shorthand for the effective concentration of the compound that inhibits 50% of viral infectivity with each of the five compounds on mammalian cells. For the results of an EC50, which are given in a molar concentration, a lower value signals a more potent compound.
The fucoidan compound RPI-27 yielded an EC50 value of approximately 83 nanomolar, while a similar previously published and independent in vitro test of remdesivir on the same mammalian cells yielded an EC50 of 770 nanomolar. Heparin yielded an EC50 of 2.1 micromolar, or about one-third as active as remdesivir, and a non-anticoagulant analog of heparin yielded an EC50 of 5.0 micromolar, about one-fifth as active as remdesivir.
The h igh activity of RPI-27 and RPI-28 relative to the other polysaccharides tested may be a result of multivalent interactions between the polysaccharide and viral particle. While heparin, TriS-heparin, and NACH are linear polysaccharides, RPI-27 and RPI-28 are both highly branched , possibly conferring added points of interaction in 3-dimensional space. The higher affinity of RPI-27 compared to RPI-28, and hence its more potent antiviral activity, may be due to the far higher molecular weight of the former providing greater opportunity for multipoint binding to the S-protein of SARS-CoV-2. 
Interestingly a separate test found no cellular toxicity in any of the compounds, even at the highest concentrations tested.
Dr Robert Linhardt, a Rensselaer Professor of chemistry and chemical biology who is collaborating with Dordick to develop the decoy strategy said, "What interests us is a new way of getting at infection. 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."
Dr Dordick added that compounds from seaweed "could serve as a basis for an oral delivery approach to address potential gastrointestinal infection."

By detailed studying of SARS-CoV-2 sequencing data, Dr Dordick and Dr Linhardt recognized several motifs on the structure of the spike protein that promised a fit compatible with heparin, a result borne out in the binding study. The spike protein is heavily encrusted in glycans, an adaptation that protects it from human enzymes which could degrade it, and prepares it to bind with a specific receptor on the cell surface.
Dr Dordick added, "It's a very complicated mechanism that we quite frankly don't know all the details about, but we're getting more information," "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."
Recent molecular modeling based on the binding study revealed sites on the spike protein where the heparin was able to interact, raising the prospects for similar sulfated polysaccharides.
The researchers say that based on the current data and studies, Fucoidan might emerge as a major game changer in the fight against the COVID-19 disease but more studies and clinical trials will be needed.
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