The PRiME Task Force on Advanced Diagnostics and Therapeutics for COVID-19

In response to the coronavirus pandemic, a highly-integrated, collaborative team has been formed to carry out critical projects with the potential to quickly impact the diagnosis and treatment of COVID-19. Researchers who are leading experts on diagnostic development, drug discovery and disease biology provide the needed skill sets for the development of new advances that will enable us to combat COVID-19 and future pandemics. 

The current members and projects of the PRiME COVID-19 Task Force are listed below and will be updated on an ongoing basis. In addition to the projects listed, a set of shared resources is under development that includes critical reagents, samples and protocols. We are looking for funding, collaborators, and partners to bolster the response to this outbreak. If you would like more information on this effort or any of the projects below, please contact us.

 
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COVID-19 Task Force Objective and Activities

Objective 1. Development of Next-Generation COVID-19 Diagnostics

High-throughput, PCR-free diagnostics as alternatives for clinical laboratories.  Achieving the necessary increases in throughput to accommodate needed levels of testing to control this pandemic will require new testing protocols that rely on a distinct set of reagents that are not currently in short supply.  Streamlined, next-generation assays are under development that can be used to quickly and accurately identify infected individuals. New approaches are being benchmarked against existing clinical assays to demonstrate clinical utility and packaged into a kit for external validation. 

Reagent-free SARS-CoV-2 detection using single-use devices to decentralize testing.  The COVID-19 pandemic has significant supply chain ramifications and the development of diagnostic testing systems that do not require any external reagents would relieve the bottlenecks that are limiting patient testing. A new family of autonomous, self-regenerating sensors are being developed to directly detect presence of the virus in clinical samples.  The approach does not require laboratory instrumentation and can be used anywhere within the healthcare system. Wearable devices for the detection of viral exposure are also under development.

New approaches for patient immunotyping for rapid assessment of COVID-19 status.  Based on the presence or absence of IgM and IgG antibodies against SARS-CoV-2, recent and past infections can potentially be differentiated.  This type of profiling is a critical tool in the fight against COVID.  Integrated assays for antibody profiling will be developed.  This capability will help detect, manage and reduce transmission of COVID-19.

Objective 2. Development of Medical Countermeasures for COVID-19 

Development of SARS-CoV-2 neutralization antibodies. Research is ongoing at UofT to quickly identify antibodies that are specific binders of SARS-CoV-2. These antibodies are important agents for diagnostics as well critical leads for therapeutic development.

High-throughput antiviral screening campaigns.  A number of new antiviral targets are being pursued to provide new options for COVID-19 treatment. Proteins involved in RNA processing, RNA synthesis and protein homeostasis are the focus of several screening efforts where compounds with prior regulatory approval will be tested for activity. 

Targeting cell surface interactions to block SARS-CoV-2 infection.  Cell surface receptors play a key role in SARS-CoV-2 infection.  Regulators of viral infection are being targeted to facilitate the development of agents that can prevent and limit pathogenesis.

Development of novel chemical scaffolds and agents targeting SARS-CoV-2.  Our task force includes several researchers developing novel chemical platforms that are promising inhibitors of viral enzymes.   Protease inhibitors and other agents are under development as first-in-class antivirals.

Screening systems for antivirals and vaccine activity.  Using engineered materials and microfluidics, groups are developing cell- and organoid-based systems for screening new COVID therapeutics and vaccines against coronavirus. 

Objective 3. Elucidating and Targeting the Biology of COVID-19

Target discovery for new COVID-19 therapeutics. New high-throughput screening technologies are being used to identify regulators of SARS-CoV-2 infection using whole genome CRISPR screening.  This effort will produce new targets for COVID therapeutic development and identify mechanisms of resistance.

Mapping virus-virus and human protein-virus interactions.  In a large-scale collaborative effort that leverages several omics modalities, proteins expressed by SARS-CoV-2 are being used for the discovery of new agents that can disrupt interactions between the virus and human cells.