Project 462582

Respiratory viruses such as SARS-CoV-2 (the virus causing COVID-19) and Influenza A virus, have inarguably had an enormous impact on human health. Although vaccines have greatly limited COVID-19 and Influenza-related hospitalizations and deaths, these viruses are continually changing, resulting in decreased effectiveness of vaccines over time. Drugs that can prevent and treat infections caused by respiratory viruses are therefore also needed. Our research teams have discovered an exciting drug that can block infections caused by multiple viruses, which we call "broadly acting antivirals". The drug, N-0385 blocks a human protease (a protein that cuts other proteins) that viruses, such as SARS-CoV-2 and Influenza A virus, take advantage of to enter the cells in our respiratory tract. In this research proposal, our aims are to further improve the pharmaceutical properties of N-0385 lead drugs, so they are more stable, easier to deliver and more suitable for animal and human drug trials. We will then measure how well these improved drugs can block SARS-CoV-2 and Influenza A virus infection in lung and other respiratory cell models when given alone or when combined. Overall, we anticipate that this research will advance these compounds so they can be further tested in clinical trials and in the future will lead to new and exciting therapeutic avenues for treatment of viruses with human pandemic potential.