Studying SARS-CoV-2 ssRNA key sequence combining Fourier transform infrared spectroscopy and theoretical folding model

Fourier transform infrared (FTIR) vibrational spectroscopy is widely used for the analysis of both protein and deoxyribonucleic acid (DNA) secondary structures, being one of the most sensitive vibrational methods to changes in molecular structure. Despite this, only few FTIR studies on ribonucleic acids (RNAs) are available. Here, we investigated a stabilized in vitro transcribed synthetic single-stranded RNA (ssRNA) from wild-type SARS-CoV-2 virus through FTIR spectroscopy and computational methods. We carried out RNA FTIR spectroscopic analysis identifying four main spectral regions of interest associated with the vibrations of sugar and phosphate backbone, base-sugar and bases. Starting from the nucleotides’ sequence, we applied two folding predictions to the ssRNA fragment, obtaining the most likely secondary and tertiary structures of the RNA fragment. These predictions have finally been compared to experimental data leading to a comprehensive structural investigation. Our results represent a step forward in understanding the structure of the SARS-CoV-2 ssRNA fragment and a promising potential starting point for sensing applications.