Spectroscopic secondary structure fingerprint of β-variant of SARS-CoV-2 spike glycoprotein

The global outbreak of COVID-19 pandemic has been accompanied by the emergence of numerous mutated forms of the SARS-CoV-2 virus, exhibiting an increasingly refined capacity to adapt to the human host. The majority of mutations affect viral proteins, particularly the Spike glycoprotein (S), leading to alterations in their physicochemical properties, in secondary structures and biological functions. In the present work, we performed, to the best of our knowledge, the first infrared spectroscopic characterization of monomeric spike glycoprotein subunits 1 (S1) of SARS-CoV-2 Beta variant at pH 7.4, combining the experimental results with Molecular Dynamic simulations, Definition of Secondary Structure of Proteins (DSSP) assignments and hydrophobicity calculations. This integrated approach has yielded valuable insights into the protein secondary structure, hydrophobic behaviour, conformational dynamics, and functional attributes, factors essential for a comprehensive understanding of the viral protein domain. Our results reveal that the SARS-CoV-2 S1 Beta variant is characterized by a secondary structure enriched with antiparallel β-sheets, as consistently supported by both experimental data and computational models. Moreover, a comparative analysis of the experimental results with hydrophobicity calculations indicates that the Beta variant exhibits a slightly more hydrophilic nature relative to the SARS-CoV-2 S1 Wild Type.