The PRiME TCAI Team Makes Significant Progress on COVID-19 Research
In April 2020, the University of Toronto was able to quickly mobilize almost $9M through the Toronto COVID-19 Action Fund (TCAI) to support over 30 high impact research projects in the fight against the global COVID-19 pandemic. Many of the members of PRiME’s Task Force on Advanced Diagnostics and Therapeutics for COVID-19 were among the recipients of this funding, and have worked tirelessly over the last year to develop novel diagnostic and therapeutic solutions to control this and future infection outbreaks.
Despite the challenges brought on by the pandemic – including, but not limited to, lab shutdowns and unstable access to essential reagents – our PRiME TCAI-funded researchers have made significant and exciting progress on their COVID-19 projects, with an unprecedented pace of development in this short period towards real world solutions. We have highlighted, below, their achievements in the past year.
Dr. Rob Batey
Dr. Batey has worked with other investigators to establish the Chemistry COVID-19 Core Facility, which will provide services and direction in synthetic and medicinal chemistry and small molecule design for COVID-19 projects in the research community.
Dr. Warren Chan
The Chan lab is using tiny light-emitting nanocrystals, known as quantum dots, in a portable, rapid diagnostic device to detect genetic components of SARS-CoV-2 in less than an hour. They are collaborating with Drs. Samira Mubareka (Sunnybrook Research Institute) and Jonathan Gubbay (Public Health Ontario) to test the device on patient swab samples, as well as fellow PRiME investigator, Dr. Gary Bader, to track how the virus is evolving so that the test can be adjusted to new variants of concern.
The test is currently still being optimized and the team will start validating the technology using patient samples. The Chan group is developing other COVID-19 technologies, including a serological test that is complete with clinical evaluation, as well as other colorimetric-based COVID-19 tests that are currently being clinically evaluated. They are also broadening to other respiratory infections, such as influenza. With all of these new diagnostics in development, the Chan lab will be partnering with Luna Nanotech, which Dr. Chan had started 4 years ago, towards commercialization. Dr. Chan is also discussing mass manufacturing of the devices and reagents with a company in Korea.
Dr. Leo Chou
With supply chain shortages plaguing the early COVID response last spring, Dr. Chou and his group want to make viral testing more streamlined and faster by using short, synthetic DNA strands in a one-step, enzyme-free test that can be deployed in a point-of-care setting. This technology is based on self-assembly of customized DNA molecules in the presence of SARS-CoV-2 viral RNA.
In partnership with the Leibniz Institute for Polymer Research Dresden and Luna Nanotech, the Chou lab received an NSERC Alliance grant for the development of this technology.
Dr. Alan Cochrane & Dr. Walid Houry
Small molecule inhibitors of virus replication are essential to treat those infected or to serve as prophylactics for those who will be exposed. Targeting cellular pathways essential to multiple strains of coronavirus can help identify therapeutic agents against current and future infectious agents. To accomplish this, a rapid screen with a library of small molecule modulators of RNA processing was performed by the Dr. Alan Cochrane’s group, and another screen of ~400 compounds targeting molecular chaperones performed by Dr. Walid Houry’s lab. To date, screening efforts have identified a handful of promising compounds that suppress SARS-CoV-2 replication.
While validation work continues, the important preclinical data from both groups is being prepared for publication. Additionally, Dr. Cochrane’s group has filed a patent on one of these compounds, and the team is currently in discussions with Virocarb, a biotech company, to obtain further funding for preclinical testing of these compounds. Dr. Houry’s group is also in the process of validating, characterizing and exploring the therapeutic potential of the lead candidates from the screen.
Dr. Aled Edwards
Dr. Edwards is leading the charge on the Toronto Open Access COVID-19 Protein Manufacturing Centre. Leveraging funding from TCAI, along with Structural Genomics Consortium (SGC) and BioZone, the protein purification team at the centre produces any of the 25 SARS-CoV-2 viral proteins for research use, free of charge and restrictions, for any Canadian business or academic. This has been an important resource for the local research community as investigators working on everything from disease biology to diagnostics to therapeutics have access to these viral components. The progress also includes development of assays to screen SARS-CoV-2 nsp14 and nsp16 protein targets, with two manuscripts published in two publications in SLAS Discovery (here and here) and one in bioRxiv.
Dr. Xinyu Liu
Dr. Liu’s team has been developing point-of-care technology for profiling the IgG and IgM antibody status of COVID-19 patients. The group recently developed a portable paper-based microfluidic platform capable of running an enzyme-linked immunosorbent assay (ELISA) in an automated, rapid (<25 min), “sample-in-answer-out” fashion. This portable platform has now been adapted to assess antibodies to SARS-CoV-2 in human patient serum.
This work has already produced one publication in Biosensors and Bioelectronics, with a second to be submitted, and has also spurred collaborations with Dr. Eleftherios Diamandis (Lunenfeld-Tanenbaum Research Institute) to work on COVID-19 rapid antigen testing, and Dr. Nicole Li-Jessen (McGill University) for rapid testing of protein biomarkers for laryngopharyngeal reflux.
Dr. Shana Kelley
The Kelley lab set out to develop a single-use device for SARS-CoV-2 detection to enable decentralized testing. This device would not require any external reagents, and thus relieve the bottlenecks that limit patient testing.
The group has made rapid advances and has published this work in the Journal of the American Chemical Society. Additionally, the handheld, reagent-free testing device to help detect COVID-19 as well as monitoring long-term disease progression is under further development by Arma Biosciences, a new Toronto-based start-up. Arma Biosciences has been part of the Creative Destruction Lab (CDL) program and was 1 of 3 winning teams out of 40 competitors at the 2020 Pitch Perfect Competition held by University of Toronto’s Health Innovation Hub (H2i). The team has also been awarded NIH funding for the further development of the sensing system.
Dr. Jason Moffat
The Moffat team has been using CRISPR to screen for gene-encoded host dependency factors on human cells for SARS-CoV-2 infection and replication. In doing so, they aim to find existing approved drugs that target these protein regulators to be repurposed for COVID-19 treatment. The screen has been completed on multiple human cell lines and a manuscript is currently in preparation.
Dr. Keith Pardee
The Pardee group has been working on PCR-free nucleic acid-based diagnostics that can serve as alternatives to current lab tests. These tests rely on a distinct set of reagents that are not in short supply, and the technology has already been extensively validated and field tested during the Zika outbreak.
This project has already resulted in two publications in BMC Biology and Nature Communications. A company, En Carta, has also been established to further develop and distribute the technology. En Carta has successfully completed the Creative Destruction Lab program and is planning to scale up the approach.
Dr. Igor Stagljar
The Stagljar lab has been working on a novel protein complementation-based assay for the serological detection of antibodies against SARS-CoV-2 in those who have recovered from COVID-19. The approach relies on complementation of proteins to antibodies, which then results in luciferase emission that can be read on a luminometer. The group worked with Sunnybrook Health Centre and Canadian Blood Services to develop their assay on blood samples of former COVID-19 patients, optimizing their test to high sensitivity and specificity for IgG antibodies. Dr. Stagljar is further validating his test by collaborating with Dr. Prabhat Jha (Centre for Global Health Research, St. Michael’s Hospital) on a study assessing long term SARS-CoV-2 immunity in thousands of Canadians, and Dr. Alison McGeer (Lunenfeld-Tanenbaum Research Institute), who is studying the effectiveness and duration of immunity in people after vaccination.
Dr. Stagljar’s assay has been published in Nature Communications, and profiled in the Globe and Mail. He is currently looking for industry partners to scale up, distribute, and make his test available to wider community.