StephanExcited to share our paper in Journal of Medicinal #Chemistry exploring carbobicyclic nucleoside analogues as potential #antivirals!
We swapped the ribose oxygen for a carbon in nucleoside analogues and explored this novel scaffold.
From our library, several compounds showed activity against #HCV, #HSV, #influenza, and #RSV. One uracil-based analogue stood out by inhibiting multiple viruses like #flu and HCV. Modeling suggests it “locks” the viral active site instead of being incorporated into RNA.
What really surprised us: nucleobases with known antiviral effects (like NHC from molnupiravir) didn’t work in our scaffold—but unmodified uracil did. The scaffold itself changes how these molecules behave.
Encouragingly, these compounds phosphorylate efficiently in cells without needing prodrugs, don't inhibit human polymerases, and our #synthesis is efficient: 28 pyrimidine and 35 purine analogues from just two intermediates in under 10 steps.
Huge thanks to all collaborators and colleagues who made this work possible!
https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c02584
J. Med. Chem. 2026, 69, 5, 5501–5539.
Stephan Hacker
Stephan Hacker
Karl Theodor
Eric the half-a-bee