Nominated Principal Applicant
Qian Liu (Vivian), McGill University
Keng Chou, University of British Columbia
Chen Liang, Lady Davis Institute for Medical Research
Our study, officially named Mechanistic understanding of the entry and transmission of SARS-CoV-2 and new variants using the single-molecule imaging technology, aims to gain a fundamental understanding of why SARS-CoV-2 variants are so transmissible and why they cause greater disease severity than the original strain. To do so, we will study anti-spike protein antibodies from the convalescent plasma of COVID-19 patients and vaccinated individuals.
To elucidate the mechanisms behind the high transmissibility of variants, we will characterize the molecular events during virus entry.
- We propose to do this by: Using single-molecule imaging technologies to unveil the SARS-CoV-2 spike protein-mediated membrane fusion process at the nanometer resolution and the millisecond scale.
- We expect to demonstrate that: it’s the spike protein in variants that increases transmission because its nanoclusters form together with its ACE2 receptor. This bond results in much faster kinetics and a unique spatial membrane distribution increasing transmissibility.
- We will pay attention to: the effect of sex and age on transmissibility by studying cell types from both males and females, and by examining convalescent plasma from all sexes and different age groups.
The knowledge gained from our study is expected to generate high-quality scientific data to accelerate the development of new prevention and treatment strategies to curb the spread of new SARS-CoV-2 variants.
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 $203,000 cash contribution.