Nominated Principal Applicant
François Jean, University of British Columbia
Mel Krajden, University of British Columbia
Ivan Robert Nabi, University of British Columbia,
Natalie Prystajecky, University of British Columbia
Theodore Steiner, University of British Columbia
Wayne Vogl, University of British Columbia
Andrea Olmstead, University of British Columbia
SARS-CoV-2 Variants of Concern (VOCs) are becoming increasingly widespread. As VOCs have the potential to spread more quickly, resist therapeutics, escape vaccine-induced immunity, and/or cause more severe disease, more research is needed to understand their biological properties (i.e., mutation rate, infectivity, and pathogenesis) and how they respond to medical countermeasures such as antiviral therapeutics.
Our study, officially named Integrated comparative phenotypic and therapeutic profiling of circulating SARS-CoV-2 Variants of Concern, brings together a research team at the University of British Columbia (UBC), which has protocols and partnerships in place to study SARS-CoV-2 VOCs at the UBC Facility for Infectious Disease and Epidemic Research (FINDER) using VOCs isolated by the BC Centre for Disease Control.
We have assembled a highly interdisciplinary team consisting of world-renowned scientists who will:
- Systematically profile SARS-CoV-2 VOC phenotypes (biological properties); and
- Investigate how VOCs react to potentially life-saving treatments.
Several strategies will be applied:
- Next-generation sequencing will be used to monitor VOC genome mutations;
- Plaque assays will be used to investigate VOC titer, plaque morphology, and plaque size;
- High-throughput bio-imaging of viral markers will be used to measure VOC level of infection and spread in two-dimensional (2D) monolayer cell culture and 3D organoid systems; and
- Fluorescence microscopy and transmission electron microscopy will be used to observe alteration of cellular and sub-cellular architecture caused by VOC infection in established cell lines and organoids.
Systematically phenotyping and screening VOCs’ susceptibility to therapeutics will support the Canadian response to the COVID-19 pandemic by contributing to our understanding of the potential of each VOC to:
- Transmit more easily;
- Engender more severe disease (pathogenesis); and
- Reduce the effectiveness of new antiviral drugs as they emerge to counteract SARS-CoV-2 associated diseases.
CoVaRR-Net is funding this research, which was first proposed to the Canadian Institutes of Health Research’s (CIHR) Emerging COVID-19 Research Gaps and Priorities – Variants funding call, with a $349,500 cash contribution.