Druggable RNA as targets for antimicrobial compounds

The latest coronavirus pandemic and the ongoing antibacterial resistance crisis highlight the need for new treatment options of pathogenic microbes.Here, we will use state-of-the-art methods to determine and verify precise secondary structures of regulatory RNAs in microbes (bacteria and virus).

The information will be used to design testable fluorophore carrying RNA constructs that mimic the native secondary RNA structure of the microbe. For bacteria, RNA constructs should encompass hairpins preventing ribosome binding and translation initiation. For coronavirus, the RNA construct will carry parts of a critical pseudoknot involved in frameshifting.

Importantly, these RNA constructs should be able to switch between an active and an inactive form. We will screen a library of ~37000 compounds to identify molecules interfering with the RNA secondary structures.

Successful compounds will be examined for their capacity to prevent bacterial virulence factor expression/infection or viral propagation.

Finally, the exact molecular target site will be determined for synthesis of compounds with increased efficacy.This work will systematically examine whether RNA could be druggable and serve as a potential target for novel antibacterial compounds. Ultimately, the work will allow for novel treatments of microbial infections.