With the first half of 2020 coming to a close, and the world still struggling with the COVID-19 pandemic, efforts to rapidly develop novel diagnostics and therapeutics continue both worldwide and locally. On June 23rd, the PRiME COVID-19 Task Force on Advanced Diagnostics and New Therapeutics held a second mini-symposium to share the latest research developments on COVID-19 projects and review new infrastructure that will improve research capacity for the current and future outbreaks.
The online symposium featured five researchers from the University of Toronto (UofT) and its affiliated hospitals who are working to understand the biology of SARS-CoV-2 infection and developing methods for better screening and monitoring of COVID-19 in the population. Dr. James Rini from the Department of Molecular Genetics (UofT), an expert on the structural biology of coronaviruses, opened the symposium with a primer on the SARS-CoV-2 spike (S) protein which binds human ACE2 receptor in the respiratory tract to cause infection and disease. Studying how the immune system targets this crucial viral entry protein can provide an advantage in vaccine development. Dr. Rini showed work from his laboratory elucidating the 3D structure of the S protein and the conformational change that occurs upon receptor binding with human ACE2. Additionally, he shared how different antibody clones – from both human and camel – can target this process in different ways for neutralization of the SARS-CoV-2 virus. Dr. Rini’s group is currently working in collaboration with Drs. Sachdev Sidhu and Alan Cochrane to develop therapeutic antibodies to treat patients with COVID-19.
Continuing the discussion on neutralizing antibodies, Dr. Anne-Claude Gingras from the Lunenfeld-Tanenbaum Research Institute (LTRI) at Mount Sinai Hospital presented her work investigating antibody seropositivity as a means of identifying individuals who have been infected with SARS-CoV-2. Using blood samples from patients obtained from Dr. Allison McGeer, Dr. Mario Ostrowski, and the Canadian Blood Services, Dr. Gingras’ group has developed three types of enzyme-linked immunosorbent assays (ELISAs) to detect neutralizing antibodies against the S protein, its receptor-binding domain, and the viral nucleocapsid. They are also profiling saliva samples in collaboration with Dr. Jennifer Gommerman and sampling large “healthy” cohorts, while also working with the National Research Council to develop a “made-in-Canada” research-grade assay for distribution to other research labs across the country.
The ability to perform wide-spread population-scale testing for COVID-19 is absolutely crucial in containing viral spread, especially as many jurisdictions in Canada and around the world are beginning to reopen their economies. However, the current qRT-PCR method of viral screening is low throughput and ill-equipped to deal with a public health crisis of this magnitude. In response to this bottleneck, Dr. Jeff Wrana from LTRI, together with collaborators from UofT, has developed a next-generation sequencing platform for high throughput PCR-based profiling of respiratory pathogens. His group has completed a proof-of-concept study and is now at the stage of optimizing the system and developing algorithms to distinguish positive from negative signals.
The final speakers of the mini-symposium were Dr. Leah Cowen and Dr. Scott Gray-Owen from the Department of Molecular Genetics at UofT. The two shared an exciting overview of new Combined Containment Level 3 (C-CL3) facilities for the University and its affiliated hospitals that will support critical research, facilitate coordination of sample collection and sharing, enhance research capacity, and expand training in infectious disease work. The expansion involves the creation of a Virology Core Facility and an Integrated Biobank in the existing C-CL3 unit on the UofT campus. These facilities will allow researchers to have a safe environment to work with highly infectious viruses, such as SARS-CoV-2, and gain access to different organismal models and systems for studying cell biology, virology, and drug efficacy. UofT’s C-CL3 facility is on its way to becoming “Canada’s facility” during this pandemic with many ongoing COVID-19 projects from both within the University and its network, as well as externally for investigators across the country.
These impressive advancements are just some of many ongoing COVID-19 projects from the Toronto research community. As we move forward into the next stage of this pandemic, we expect to see many innovations and technologies being developed in our community emerging as solutions to resolve this global crisis.