SFU Chemists Develop Light-Driven Method to Rapidly Generate Nucleoside Analog Libraries, Accelerating Antiviral Drug Discovery
核心洞察
Simon Fraser University researchers published a new method in *Science* that uses a light-driven reaction to rapidly generate large libraries of nucleoside analogs (搜索) from a single scalable building block.
The approach can produce compound libraries 10 to 100 times larger in weeks rather than months or years, dramatically accelerating early-stage antiviral drug discovery.
Screening the library against HIV (搜索) identified three compounds with activity comparable to approved HIV therapies, with most compounds being entirely new.
Simon Fraser University researchers have unveiled a novel chemical method that promises to dramatically shorten the timeline for antiviral drug discovery. Published in Science, the study describes a light-driven approach that enables the rapid generation of large libraries of nucleoside analogs (搜索) (NAs) — compounds that mimic the building blocks of DNA and RNA and are widely used to treat cancer and viral infections such as HIV (搜索) and hepatitis.
"This is a game changer for making and modifying nucleosides," said Robert Britton, chemistry professor 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."
Addressing a Critical Gap in Antiviral Development
Britton underscored the urgency driving the research, noting the disparity between available treatments for different disease categories. "We have lots of pain killers and a wide collection of antibiotics, but we don't have a good panel of antivirals, which is why viral outbreaks like COVID-19, or Ebola, or hantavirus scare people so much," he said. "Finding viable drug candidates is extremely challenging."
In traditional drug discovery, scientists screen libraries of molecules to identify promising "hits" for further development — an approach that helped companies like Merck & Co. (搜索) and Gilead Sciences develop early COVID-19 treatments. However, generating sufficiently large molecular libraries for antiviral screening has historically been constrained by complex and time-consuming chemistry.
A Light-Driven, Scalable Platform
The SFU team, which included scientists from Merck, addressed this bottleneck by starting with a single, scalable building block — one versatile molecular starting point that can be produced in large quantities. Using a light-driven reaction, the researchers attached different nucleobases to this core structure, rapidly generating a library of more than 70 nucleoside analogs (搜索).
To validate the approach's practical utility, the team screened the resulting library against HIV (搜索). Three compounds demonstrated activity comparable to approved HIV therapies, confirming that the method can yield biologically relevant drug candidates.
"Most of the compounds in our library were entirely new," Britton noted. "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."
Implications for Future Outbreak Response
The ability to generate compound libraries 10 to 100 times larger in a fraction of the time could prove transformative in responding to emerging viral threats. By dramatically reducing both the time and resources required for early-stage drug discovery, the platform positions researchers to screen more candidates more quickly — a critical advantage when confronting novel or rapidly evolving pathogens.