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As the world faces new and often untreatable viral threats, Simon Fraser University researchers have found a way to cut years off the time it takes to discover antiviral drugs. The new research enables scientists to quickly create large libraries of nucleoside analogs (NAs), compounds that mimic the building blocks of DNA and RNA and are widely used to treat cancer and viral infections such as HIV and hepatitis.
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The new method could significantly reduce the time and resources needed for early-stage drug discovery. The study is published in the journal Science.
"This is a game changer for making and modifying nucleosides," explains Robert Britton, professor of chemistry and lead author of the study. "In an emerging outbreak, the more compounds you can screen, the better your chances of finding something effective. With this method, we can produce libraries 10 to 100 times larger in just weeks, rather than months or years."
"We have lots of painkillers and a wide collection of antibiotics, but we don't have a good panel of antivirals, which is why viral outbreaks like COVID-19, Ebola or hantavirus scare people so much," says Britton. "Finding viable drug candidates is extremely challenging."
To identify new treatments, scientists typically screen libraries of molecules to find promising "hits" for further development. This approach helped companies like Merck & Co. and Gilead Sciences develop early COVID-19 treatments.
But in antiviral discovery, scale matters. Generating large libraries of molecules to screen has been limited by complex chemistry.
In the study, Britton and his research team, which included scientists at the drug company Merck, began with a single, scalable building block—one versatile molecular starting point that can be produced in large quantities.
Using a light-driven reaction, the team attached different nucleobases to this core structure, quickly generating a library of more than 70 NAs.
To test whether the approach could find useful drug candidates, the researchers screened the library against HIV. Three compounds showed activity comparable to approved HIV therapies.
"Most of the compounds in our library were entirely new," Britton says. "A few had been made before, but it took other groups longer to synthesize those molecules, and they were not able to modify and improve them as readily."
More information: Matthew J. Anketell et al, A unified platform for nucleoside analog synthesis, Science (2026). DOI: 10.1126/science.aed6880
Provided by Simon Fraser University
This story was originally published on Phys.org.
