Breaking the weakest link: Broad-spectrum drugs against RNA viruses

Discovery of pan-corona antivirals and characterization of the structure-function relation between antiviral compounds and viral proteases Viruses have crossed from animals to humans with high mortality rates in recent years and we can expect further crossings to happen over the next few decades. To avoid future pandemics as experienced during the SARS-CoV2 breakout, we must develop preemptive pan-coronavirus orally available drugs for a wide range of viral protection. This can only be done if we better understand how small molecules can inhibit viral autoproteases, such that we can create compounds used as an initial response to viral breakouts. We will investigate the power of a pre-existing small molecule library for their effect on viral proteases from all beta-corona lineages. To achieve this I will engineer a luminescence-based multi-protease reporter system, that allows for direct comparison of pan-corona protease inhibition. Then by collaboration, we will use structure-based, AI-assisted screens, to enhance inhibition, efficacy, and potency toward multiple targets.