In a test of antiviral effectiveness against the virus that causes COVID-19, an extract from edible seaweeds substantially outperformed remdesivir, the current standard antiviral used to combat the disease. 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.
Published in Cell Discovery, the research is the latest example of a decoy strategy researchers from the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselear Polytechnic Institute, where scientists are developing solutions against viruses like the novel coronavirus that spawned the current global health crisis.
The 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.
The Cell Discovery paper tests 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 researchers performed a dose response study known as an EC50 — shorthand for the effective concentration of the compound that inhibits 50 percent 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.
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. A separate test found no cellular toxicity in any of the compounds, even at the highest concentrations tested.
