A medicinal chemistry study investigated a new class of nucleoside analogues built on a synthetically accessible carbobicyclic scaffold designed to conformally mimic ribose. The researchers found that library screening revealed pan-antiviral activity against several viruses, including HCV, HSV, and influenza. Specifically, the uracil analogue 2a inhibited influenza A virus replication by directly disrupting viral polymerase activity. Metabolism analysis suggested that the compounds did not require complex prodrug formulations; instead, they are readily phosphorylated into active triphosphates that bypass human polymerases, avoiding toxicity. The findings suggest this novel architecture provides a promising chemotype for safer pan-antiviral therapeutics.

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