A sugar present on virus envelopes might become the target of new antiviral treatments for a range of viruses, researchers report August 27 in Science Advances. This treatment, shown to shut down infections of Ebola, Nipah, SARS-CoV-2 and other viruses in mice, could potentially be the first line of defense against future pandemics, the scientists say.
“This is an interesting study, showing a possible pathway towards broad-spectrum antivirals,” says William Wimley, a biochemist at Tulane University School of Medicine in New Orleans, who wasn’t part of the study. “But there are still many optimization steps before we get there.”
Broad-spectrum antivirals are tricky to make because viruses mutate quickly, making it hard to develop a drug that works against different viruses, even those within the same family.
In the new study, biochemist Adam Braunschweig and his colleagues focused on N-glycans, sugar molecules on the surface of virus membranes that help them attach to and break into host cells. Preventing the glycan from attaching to the virus could prevent it from entering the cell, replicating and spreading.
“These sugars are all attached to the virus using the same exact molecule as a linker,” says Braunschweig, of the City University of New York. “We created molecules that targeted that linker.”
Braunschweig’s team tested 57 synthetic carbohydrate molecules that might slot into the receptor used by the glycan molecules to fuse with viral particles. Four did the trick.
The team then measured whether the molecules were effective in impeding the virus in living primate cells. The found that preventing this sugar–virus fusion successfully blocked cell infection from six viruses — Ebola, Hendra, Marburg, Nipah, SARS-CoV-1 and SARS-CoV-2 — from three unrelated families.
The researchers also tested mice infected with SARS-CoV-2, the virus responsible for COVID-19. In a series of tests on eight to 10 mice, they offered the new carbohydrate molecules as treatment. With a single dose, 90 percent of the infected mice survived, compared with none in the control group.
The scientists have since expanded their testing, including adding three more viruses to their list. They expect to move these molecules into clinical trials in 2028. The mechanism for binding surface glycans could also be leveraged for treating cancers and immunological disorders, Braunschweig says.
On August 13, researchers at Columbia University also reported a broad-spectrum antiviral that uses mRNA to make host cells produce a protein with antiviral properties. “Maybe this is ushering in a new area of broad-spectrum antivirals,” Braunschweig says.
Wimley, however, cautions that there’s work to be done, specifically with the potency and range of action of these molecules before they can be developed into therapeutics. “Most importantly, we need to know how quickly viruses will develop resistance.”
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