Synthesis of Strongly Pairing C-Nucleotides

成功的治疗是控制病毒大流行的最重要因素之一。当以功能保守的酶为靶点时，治疗学可以提供不依赖于遗传变异的结果。对于RNA病毒和逆转录病毒，依赖于RNA的RNA聚合酶(RdRp)和逆转录酶分别是主要的靶标。具有活性的三磷酸形式的核苷类似物可以有效地抑制病毒复制。本项目致力于合成新的核苷类似物及其磷酸化衍生物。在现有C-核苷嘧啶类似物和磷酰胺的专业知识的基础上，将使用系统的方法来设计和合成与模板中的核苷酸碱基配对很强的新的核苷类似物。将研究与模板-底物复合体的结合和前药形式的释放，并将使化合物可用于生物试验。预计这一结果将产生新的抗病毒候选药物，以应对目前和未来由病毒造成的健康挑战。

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.