Abstract
The contagiousness of SARS-CoV-2 β-coronavirus is determined by the virus-receptor electrostatic association of its positively charged spike (S) protein with the negatively charged angiotensin converting enzyme-2 (ACE2 receptor) of the epithelial cells. If some mutations occur, the electrostatic potential on the surface of the receptor-binding domain (RBD) could be altered, and the S-ACE2 association could become stronger or weaker. The aim of the current research is to investigate whether point mutations can noticeably alter the electrostatic potential on the RBD and the 3D stability of the S1-subunit of the S-protein. For this purpose, 15 mutants with different hydrophilicity and electric charge (positive, negative, or uncharged) of the substituted and substituting amino acid residues, located on the RBD at the S1-ACE2 interface, are selected, and the 3D structure of the S1-subunit is reconstructed on the base of the crystallographic structure of the S-protein of the wild-type strain and the amino acid sequence of the unfolded polypeptide chain of the mutants. Then, the Gibbs free energy of folding, isoelectric point, and pH-dependent surface electrostatic potential of the S1-subunit are computed using programs for protein electrostatics. The results show alterations in the local electrostatic potential in the vicinity of the mutant amino acid residue, which can influence the S-ACE2 association. This approach allows prediction of the relative infectivity, transmissibility, and contagiousness (at equal social immune status) of new SARS-CoV-2 mutants by reconstruction of the 3D structure of the S1-subunit and calculation of the surface electrostatic potential.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.