Sho Iketani, PhD

COVID-19 remains an ongoing issue with continued illness and death. While we have gained significant understanding of the biology of the SARS-CoV-2 virus and have developed effective vaccines and therapeutics, there still remains much left unknown about the virus. One challenge in studying the virus has been the difficulty in running large-scale experiments of the virus itself. We will develop an approach that allows us to systematically study the functions of the virus’ proteins. While the data that we generate should be valuable for understanding SARS-CoV-2 and for developing new treatments against this virus, the methods that we build should be applicable to other viruses and diseases such as cancer. Therefore, although SARS-CoV-2 will be used as a model, our research has the potential to have a much wider impact.

Supported by the Mary Fuller Russell Fund

Update: We have focused on an essential viral protein called the RNA-dependent RNA polymerase, which SARS-CoV-2, the virus that causes COVID-19, requires for replication. Using a powerful technique called deep mutational scanning, we tested nearly every possible single genetic change in one important region of this protein, successfully measuring the effects of 1,638 mutations. Most of the mutations weakened the virus, as would be expected for a protein that is critical for SARS-CoV-2 survival. Some mutations, however, had little effect on replication, providing new clues about how the virus can evolve over time. The team plans to expand this work to study the entire gene and to examine how combinations of mutations affect the virus. This is the first time researchers have been able to perform this type of large-scale genetic analysis directly in SARS-CoV-2. The findings will improve our understanding of how the virus mutates and may help scientists identify new targets for antiviral drugs and prepare for future coronavirus variants.