Dynamic evolutionary forces shaping the SARS-Cov-2 receptor binding domain 2874

Abstract Description Understanding the evolution of viruses is critical for developing effective strategies to combat a future pandemic. For example, the emergence of different SARS-CoV-2 variants, driven by mutations in the viral genome, has led to significant changes in transmission rates, virulence, and vaccine effectiveness. These mutations occur naturally as the virus replicates, with certain variants gaining an advantage through increased transmissibility or the ability to evade immune responses. To navigate this evolving landscape, genetic changes that contribute to these adaptations are being examined. Mapping out the evolutionary landscape of the SARS-CoV-2 spike protein is our central focus. By artificially generating many spike protein combinatorial variants in the receptor binding domain, we assay their binding affinities to the ACE2 receptor using in vitro translation and affinity capture methods, including deep sequencing of the co-captured mRNA molecules. The ACE2 receptor is key to the virus’s ability to infect human cells. We use this binding affinity as a measure of the virus’s fitness, providing insights into how specific mutations influence the evolutionary success of different variants. The outcomes of this work may guide future efforts to control the spread of other viruses by enabling a better understanding of molecular evolution. Funding Sources This work is supported by NIH. Topic Categories Viral Immunology (VIR)