Reverse genetic analysis of mechanisms underlying convergent evolution of SARS-CoV-2 variants of concern and accessory protein functions

The response to COVID-19 pandemic has been a triumph of science. At the beginning of the pandemic humans had no defense against SARS-CoV-2 and within a year effective vaccines and mass vaccination efforts have allowed society to reopen. However, the pandemic continues unabated despite the introduction of modified vaccines and regular vaccine boosting due to the emergence of new variants and continued evolution of the virus. The emergence of more viral variants is inevitable and continued waves of SARS-CoV-2 infections through world human population could pressure the emergence of new and potentially dangerous viruses. Worldwide surveillance identifies viruses having genome sequence changes, but which sequence changes lead to a dangerous virus and which are benign remain unknown. In addition, several sequence changes appear to have evolve many times independently. This process is called convergent evolution and is thought to be a product of positive selection where advantageous mutations accumulate and become prevalent. This proposal aims to identify mechanisms underlying convergent evolution of mutations in SARS-CoV-2 variants of concern by studying how individual or groups of mutations affect the replication, spread, and pathogenesis of SARS-CoV-2. Our goal is to identify mutations that signify a potentially dangerous variants to inform public health, vaccine and treatment decisions, and global efforts prevent the spread of disease.