Epidemiological, clinical, and functional characterization of genomic variation in SARS-CoV-2

Coronavirus Disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has now become a global pandemic that is expected to sicken millions of people and seriously curtail the global economy. Whole-genome sequencing is a vitally important tool for understanding how this virus is able spread and cause disease in humans. We propose to sequence the genomes of over 300 SARS-CoV-2 viruses that have caused infections across the Chicago area. By comparing these virus sequences to others across the city, the country, and the world, we will better understand how the immune system is driving the virus to adapt. We will use clinical information from infected patients to determine whether particular gene mutations correlate with infection severity. We have observed that mutations in the SARS-CoV-2 gene Nsp13 are present in most viruses causing infections in the USA to date, but are rare in other countries. We will explore the effect of these mutations on the protein encoded by this gene, specifically the interaction of the protein with cultured human cells and with antiviral medications. Together these studies will increase our understanding of function and transmission of SARS-CoV-2 and open the door to studies into new diagnostics and therapeutics for COVID-19.