Studies are in early stages, according to the scientists at Rensselaer Polytechnic Institute (RPI) leading them.
With widespread immunity against SARS-CoV-2 within the general population increasingly unlikely, researchers instead want to address the elephant in the room.
That being the fact that the coronavirus looks as if it’s here to stay. Thus, better management of it is vital.
To date, several avenues have been explored, from convalescent plasma to remdesivir, an antiviral originally developed to treat Ebola. Hydroxychloroquine, of course, had its moment in the sun—that is, until clinical trials revealed that it provided no benefit—and significant risk—when used to treat patients hospitalized with COVID-19.
However, one research direction that thus far at least has shown promise involves an age-old strategy called “viral decoy,” which has offered some degree of success as part of efforts to combat dengue, Zika, and influenza A. In their explorations of this approach, researchers from RPI have found that variants of the blood-thinner heparin and compounds derived from edible seaweeds substantially outperforms remdesivir as a treatment for COVID-19.
“The way the decoy strategy works is by tricking the virus to bind to the decoy instead of specific molecules on the surface of target human cells,” Jonathan Dordick, PhD, one of the lead researchers on the project a professor of chemical and biological engineering at RPI, which is in Troy, NY, told Contagion. “We believe that SARS-CoV-2 recognizes specific polysaccharides on the cell surface known as heparan sulfates, [which] appear to position the virus to then bind to the ACE2 receptor and that leads to infection.”
In a dose response study published last summer by Cell Discovery, Dordick and his colleague, Robert Linhardt, PhD, a professor of chemistry and chemical biology, along with others, tested antiviral activity of 3 variants of heparin—heparin, trisulfated heparin, and a non-anticoagulant low molecular weight heparin—and the 2 fucoidans extracted from seaweed—RPI-27 and RPI-28. Dr. Linhardt is credited with the creation of synthetic heparin. According to Dordick, all 5 compounds are long chains of sugar molecules known as sulfated polysaccharides, a structural conformation that makes them potentially effective as a decoy.
In the study published last summer, which used mammalian cells infected with SARS-CoV-2, RPI-27 had an EC50 value of roughly 83 nanomolar, while the heparin variants produced EC50s ranging from 2.1 micromolars to 5.0 micromolars. In comparison, earlier studies of remdesivir on the same mammalian cells yielded an EC50 of 770 nanomolar. In addition, both heparin and the non-anticoagulant low molecular weight heparin performed similarly to remdesivir in inhibiting SARS-CoV-2 infection in the mammalian cells used in the study. Both compounds bind tightly to the spike protein on the surface of SARS-CoV-2 “and block these spikes from accessing the ACE2 receptor,” Dordick said.
“The ability of the virus to infect cells is dramatically diminished,” he added.
The team is now developing a way for these compounds to be delivered to human trial subjects via a nasal spray and/or aerosol pulmonary delivery, for use not just against SARS-CoV-2 but influenza and other respiratory viruses as well.
“Antiviral therapy remains complex—there are very few antivirals that are able to work well,” Dordick said. “Having something that, for example, can be a prophylactic may be a very interesting concept. We are currently working on heparin and heparin analogs as components of a nasal spray, which could be taken before or at the earliest signs of infection. In all antivirals, if you can use them quickly and early, the chance of reducing the severity of infection goes way up.”