A novel coronavirus (SARS-CoV-2) emerged in Hubei, China in December 2019 and has since spread rapidly to become a global pandemic. There is a critical need for fundamental research on the biology of this virus and its interactions with the human host to stem the spread of the disease and mitigate its devastating impacts on the global human population. The research supported through this RAPID award will enhance knowledge of how this virus evolves, and it may provide vital clues about its interactions with the human host. Previous research has shown that a critical region of the viral genome is highly conserved, harboring very few mutations compared to the rest of the genome. Exploring the underlying basis for this sequence conservation will reveal new information on factors that could influence the spread, diagnostics and treatment of SARS-CoV-2. The project also offers training opportunities for graduate and undergraduate students, and will support development of a web-based tool for the community to study viral genome evolution.
The PI has identified a region of the SARS-Cov-2 genome, which includes the RNA-dependent RNA polymerase (RdRp), which has extremely high conservation at the nucleotide level. This finding suggests that selection is acting to maintain sequence motifs in this region, possibly pointing to structural constraints on the RdRp RNA or RNA-mediated interactions between the virus and host. The project will explore a range of hypotheses about selection factors, including noncoding RNAs, RNA secondary structure and RNA binding sites for host proteins, among others, that could account for the sequence conservation. The project will also attempt a study relating these factors to human susceptibility to SARS-CoV-2, if access is gained to patient data on genome variation and corresponding infection severity.
This RAPID award is funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
