Optimisation of a triterpene lead compound for the development of pan-anticoronavirus drugs targeting nsp15

Antiviral drugs against coronaviruses (CoVs) are urgently needed, preferentially in the form of a pan-coronavirus inhibitor that would cover both human and animal CoV species. We have recently established a triterpene derivative as an inhibitor of nsp15, thus halting RNA synthesis. In this project, it is our objective to design and synthesize analogs bearing diverse structural variations, that will be subjected to a structure-activity relationship (SAR) study against nsp15, with the ultimate goal to discover compounds with pan-anticoronavirus activity. Thus, we will firstly identify novel synthetic pathways towards different triterpene analogs. Then we will gather biological results against nsp15 and rationalize the specific interactions with nsp15 via docking experiments. Finally, based on the SAR data we will investigate non-triterpene analogs that possess more “drug-like” characteristics. This will lead to a library of compounds with their complete biological activities and docking information.