Abstract 2075 Finding an RNA Aptamer against COVID S-Protein for the Development of a Treatment

The SARS-CoV-2 virus is the pathogen at the root of the COVID-19 pandemic, a global emergency that has caused over 770 million infections and 6.9 million deaths (WHO Coronavirus (COVID-19) Dashboard, n.d.). Despite treatments being proposed, including hydroxychloroquine (Schwartz et al., 2022), none were found to be reasonably effective against SARS-CoV-2, thus more options are needed. One such potential treatment could be in the form of an aptamer therapeutic. Aptamers, or sequences of oligonucleotides that can bind specifically to a target, are recommended against the COVID S-Protein S1 subunit due to their target specificity and ease of chemical conjugation. We propose creating a multi-aptamer complex that targets the SARS-CoV-2 spike protein (COVID S-Protein) S1 subunit through the use of an anti-COVID S-Protein aptamer and initiates an immune response. Specifically, the anti-S-Protein aptamer will be conjugated to an anti-macrophage aptamer, eliciting an immunogenic attack of the virus by the macrophage, and thereby successful treatment of the disease. The initial aim of this research is to identify a suitable RNA aptamer against COVID S-Protein in humans using the Systematic Evolution of Ligands by Exponential Enrichment (SELEX). SELEX involves a three-step process: binding and selection, amplification, and purification. Specifically, a N71 RNA pool is incubated with the COVID S-Protein, unbound RNA sequences are washed away, and the S-Protein-bound RNA sequences are amplified, enriching the pool ideally for S-Protein-binding sequences. This process will be repeated over approximately 15 cycles, allowing us to isolate potential aptamers. The anti-S-Protein aptamer will then be conjugated to the anti-macrophage aptamer to create the therapeutic aptamer complex to induce an immune response. To date, the third round of approximately 15 rounds of selection has been initiated. Future rounds would increase stringency conditions in order to find the most suitable aptamer in physiological conditions. Identification of such an anti-S-Protein aptamer would put us on the path to developing an aptamer complex to potentially treat patients with COVID. I sincerely thank the University of Texas at Austin Freshman Research Initiative, as well as the College of Natural Sciences, for their support in this research.