Mutations in the SARS CoV-2 spike protein may cause functional changes in the protein quaternary structure

ABSTRACT

Objectives: This study aimed to model the changes resulting from mutations in surface (spike/S) glycoproteins, which play a key role in the entry of the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) into host cells, in a protein quaternary structure and to evaluate their possible effects on the functional structure. Methods: Genome sequence information of SARS CoV-2-infected patients located in Turkey was obtained from the GISAID EpiCoV database. Structural analysis of spike proteins was done using bioinformatics tools (MAFFT, PSIPRED, ProMod3, PyMoL and DynOmics). Results: We identified 76 Thr>Ile mutations in the N-terminal domain;468 Ile>Val mutations in the receptor binding site and 614 Asp>Gly, 679 Asn>Lys, 771 Ala>Val and 772 Val>Ile mutations in the S1 subunit. It has been observed that the mutations, except those of residues 771 and 772, may cause significant conformational, topological and electrostatic changes in a protein quaternary structure. It has been determined that the mutations in the receptor binding site transform the protein structure into a formation that can mask the binding site and affect receptor affinity. Conclusions: It has been considered that SARS CoV-2 S glycoprotein mutations may cause changes in a protein functional structure that can affect the severity of disease.