The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), highlights the urgent need for predictive tools and preparedness strategies. Deep Mutational Scanning (DMS) libraries offer a promising approach to anticipating future viral evolution. In this study, we used a DMS viral library of the SARS-CoV-2 Omicron BA.5 strain as a base to create three separate libraries: Spike N-terminal domain (NTD), Receptor Binding Domain (RBD), and a combined library covering both regions (NTD-RBD). The diversity of the generated DMS libraries was confirmed through Nanopore deep-sequencing of the intermediate vectors and the infectious viral libraries. Each library was inserted into infectious clones or CPER assembled to produce viral libraries. Passage of mutated viruses resulted in enhanced viral fitness due to specific mutations within the Spike protein's mutated regions. Our findings underscore the potential of DMS libraries in predicting viral evolution, thereby contributing to our preparedness for future pandemics. We will examine neutralization escape mutations using known neutralizing antibodies and sera from vaccinated and infected patients with SARS-CoV-2. The results of this study are expected to forecast new variants based on coronavirus Spike protein evolution and aid in the preparation of vaccine candidates.