New Antiviral Compounds

Drug repurposing has been proposed as a shortcut towards developing antivirals. However, there are limitations to this concept, including pharmacokinetics/pharmacodynamics (PK/PD), the low probability of drugs highly optimized for one target having pharmacologically relevant activities against others, and their pharmacological effects precluding safe use in other diseases.
Chemists at the University of Alberta have re-engineered existing drugs based on smaller, simpler scaffolds to develop antivirals of broad spectrum. The resulting compounds were tested at Cornell University for anti-viral activity. Two compounds were selected for their activity against HCoV-OC43 and human coronaviruses in viral replication assays; these showed low potency and low selectivity. An initial exploration of the chemical space identified a lead scaffold that produced compounds preserving the potency while decreasing toxicity. Second generation compounds have shown single digit micromolar potency and selectivity indexes larger than 10 to 20 (the highest concentration tested, 100 μM, did not result in 50% cytotoxicity). These compounds are active against two distantly-related coronaviruses and provide a scaffold for development based on a clinical drug. We are testing their activities against other viruses and studying mode of action.