Synthesis of Strongly Pairing C-Nucleotides

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Successful therapy is one of the most important factors in bringing viral pandemics under control. Therapeutics can deliver results independent of the genetic variant, when functionally conserved enzymes are targeted. For RNA viruses and retroviruses, the RNA-dependent RNA polymerase (RdRp) and the reverse transcriptase are prime targets, respectively. Nucleoside analogs in their active triphosphate form can be potent inhibitors of viral replication. This project is focused on the synthesis of new nucleoside analogs and their phosphorylated derivatives. Building on existing expertise with C-nucleosidic pyrimidine analogs and phosphoramidates, a systematic approach will be used to design and synthesize new nucleoside analogs that pair strongly with nucleobases in the template. Binding to template-primer complexes and the release from prodrug forms will be studied and compounds will be made available for biological tests. The results are expected to produce new antiviral candidates for combating current and future health challenges caused by viruses.