Search for structural differences in spike glycoprotein variants of SARS-CoV-2: Infrared Spectroscopy, Circular Dichroism and Computational Analysis

The SARS-CoV-2 pandemic has led to a significant emergence of highly mutated forms of viruses with a great ability to adapt to the human host. Some mutations resulted in changes in the amino acid sequences of viral proteins, including the Spike glycoproteins, affecting protein physico-chemical properties and functionalities. Here, we propose, for the first time to the best of our knowledge, a systematic and comparative study of the monomeric spike protein subunits 1 of three SARS-CoV-2 variants at pH 7.4, combining both an experimental approach, taking advantage of Attenuated Total Reflection Infrared and Circular Dichroism spectroscopies, and a computational approach via Molecular Dynamics simulations. Experimental data in combination with Molecular Dynamics and Surface polarity calculations provide a comprehensive understanding of variants proteins in terms of their secondary structure content, 3D conformational structure and order and interaction with the solvent. The present structural investigation clarifies which kind of changes in conformation and functionalities occurred as long as mutations appeared in amino acids sequences. This information is essential for preventive targeted actions, drug design, and biosensing applications.