Project 443334

SARS-CoV-2 (the causative agent of COVID-19) poses a generational threat, with no licensed vaccines or effective therapies to date. Further, the scarcity in reliable diagnostics, especially when testing asymptomatic/mildly symptomatic cases, is of grave concern. Accordingly, our proposal tackles 2 of the 3 research areas of this call, and addresses all 5 objectives, by developing and testing SARS-CoV-2 therapeutics and also prototyping convenient point-of-care (POC) COVID-19 diagnostics with scaling-up feasibility. For the therapeutic arm, we will innovatively design and test peptide disruptors of the SARS-CoV-2 spike (S) glycoprotein interaction with the human ACE2 receptor during viral entry, and other peptide inhibitors of viral-human interactions required for SARS-CoV-2 establishment. These will be tested in vitro using cell-based assays, with promising disruptors validated in SARS-CoV-2 hamster models. In addition, we will screen our in-house synthetic compounds targeting chaperones as potential SARS-CoV-2 replication inhibitors in both cell-based assays and animal models. On the diagnostic front, we will develop new diagnostic solutions for effective detection of even mild/asymptomatic SARS-CoV-2 carriers at home and/or in remote locations. This POC lab-on-a tip technology will specifically detect SARS-CoV-2 peptides from patient saliva, with our clinician collaborators taking the lead in scaling-up both peptide therapeutics and our POC diagnostic device through ongoing coordination with the federal government and Saskatchewan Health Authority. This proposal brings together leading Canadian scientists and clinicians to fulfill our objectives by generating high-quality data to diagnostically and therapeutically accelerate the detection and prevention of COVID-19 and foster nationwide collaborations, with a clear scaling-up path that will refine decision-making across Canadian jurisdictions for effective and timely containment of the COVID-19 outbreak.