Mutation-Induced Changes in the Stability, B-Cell Epitope, and Antigenicity of the Sars-Cov-2 Variant Spike Protein: A Comparative Computational Stud

Nira Meirita Wijayanti, Biology Department, Faculty of mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia
Muhammad Hermawan Widyananda, Biology Department, Faculty of mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia
Lailil Muflikhah, Department of Informatics Engineering, Faculty of Computer Science, Brawijaya University, Malang, Indonesia
Nashi Widodo, Biology Department, Faculty of mathematics and Natural Sciences, Brawijaya University, Malang, IndonesiaFollow

Abstract

The spike (S) protein is a major antigenicity site that targets neutralizing antibodies and drugs. The growing number of S protein mutations has become a severe problem for developing effective vaccines. Here, we investigated four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that were the most infectious and widespread during the COVID-19 pandemic to determine the trends and patterns of mutation-induced changes in the stability, B-cell epitope, and antigenicity of the SARS-CoV-2 S protein. The data showed that the Beta and Gamma variants had three mutations on the receptor-binding domain (RBD), which is the specific site on the S protein for angiotensin-converting enzyme 2 (hACE2) binding. The Delta variant had only two mutations, whereas the Omicron variant had 15 mutations on the RBD. The results showed that the stability of the S protein varied and depended on the mutation type and that Gamma and Omicron are the most stable of the four variants analyzed. The S protein–hACE2 complexes of the Beta and Gamma variants were relatively stable after 20 ns of simulation compared with those of the Delta and Omicron variants. We predicted that the B-cell epitopes of the mutant S protein would be different from those of the wildtype. Moreover, the antigenicity of Omicron changed drastically compared with that of the other variants. Bioinformatics analysis and a molecular dynamic simulation revealed that the mutations affected the stability of the S protein. A large number of mutations do not always stabilize the S protein. Mutations in Omicron significantly altered the B-cell epitope and antigenicity, which decreased vaccine effectiveness. These findings provide insights into SARS-CoV-2 evolution for vaccine development.

Recommended Citation

Wijayanti, Nira Meirita; Widyananda, Muhammad Hermawan; Muflikhah, Lailil; and Widodo, Nashi (2023) "Mutation-Induced Changes in the Stability, B-Cell Epitope, and Antigenicity of the Sars-Cov-2 Variant Spike Protein: A Comparative Computational Stud," Karbala International Journal of Modern Science: Vol. 9 : Iss. 3 , Article 12.
Available at: https://doi.org/10.33640/2405-609X.3311