Rapid development of antiviral compounds to fight the COVID-19 outbreak [Added supplement: COVID-19 Variant Supplement]

The outbreak of a respiratory illness (COVID-19) in China at the end of December 2019 has been demonstrated to be caused by a new coronavirus. While health officials are using quarantine methods to try and prevent the spread of the infection, there are currently no treatments for the illness, which can be severe and even lead to death in 2% of cases. Here, we propose to build on our previous research with viruses of the same family, which include those that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). We have previously successfully engineered small proteins capable of blocking the activity of an enzyme of the virus that is crucial for its replication and for shutting down the human immune response. We plan on using a similar strategy to build blockers of the new virus. These will be extremely useful in better understanding the biology of the virus. Most importantly, we will use these blocking proteins to find chemical drug candidates that block the activity of the viral enzyme in infected cells, which can then be developed as therapeutics. Our method is rapid and cost efficient, and within the two years of this grant, we expect to have a number of lead candidate drugs. In order to achieve these goals, we have assembled a team of leading scientists with expertise in protein engineering of viral inhibitors (Sachdev Sidhu, University of Toronto), structural biology of viruses (Brian Mark, University of Manitoba), and development of chemical drugs (Roman Melnyk, SickKids Research Institute, Toronto). Our project also has the support of an internationally recognized leader in viral biology (Marjolein Kikkert, Leiden University, Netherlands) and a frontline clinician-scientist in infectious diseases (Samira Mubareka, Sunnybrook Health Centre, Toronto). Ultimately, this work will generate critical tools to better understand this new virus, and most importantly, will provide novel candidate drugs for direly needed therapies.