Structural differences in protein domains of SARS-CoV-s Spike glycoprotein induced by mutations: infrared spectroscopy, circular dichroism and computational analysis

Virus spreading generally leads to the occurrence and diffusion of mutations in viral genomic sequences, and therefore to changes in the viral transmissibility and infectivity, producing more adaptive and resistant species. Going to a molecular level, the study of viral mutations and how they influence both the structure, and the physico-chemical properties of virus structural proteins can be of deep interest for drug design, biosensing application and preventive targeted actions. Considering the recent SARS-CoV-2 pandemic, this has led to a significant emergence of highly mutated forms of viruses with a great ability to adapt to the human host [1]. Some mutations resulted in changes in the amino acid sequences of viral proteins, including the Spike (S) glycoproteins [2]. In this work we propose, for the first time to the best of our knowledge, a systematic and comparative study of the monomeric S protein subunits 1 of three SARS-CoV-2 variants, Alpha, Gamma and Omicron variants, differing for 7, 14 and 31 mutations, respectively. Both experimental and computational approaches have been employed, combining Attenuated Total Reflection Infrared (ATR-IR) and Circular Dichroism (CD) spectroscopies, which are well-established experimental methods for a noninvasive analysis of polypeptides and proteins [3,4], with Molecular Dynamics (MD) simulations and protein Surface Polarity Calculation. Experimental data in combination with computational results, provide a comprehensive understanding of SARS-CoV-2 variants’ proteins in terms of their secondary structure content, 3D conformation and interaction with the solvent [5]. This structural investigation aims to clarify which kind of changes in structure and functionalities occurred as long as mutations appeared in amino acids sequences, providing potential and important information for the development of therapeutic protocols and monitoring strategies.