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.
Wijayanti, Nira Meirita; Widyananda, Muhammad Hermawan; Muflikhah, Lailil; and Widodo, Nashi
"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
, Article 12.
Available at: https://doi.org/10.33640/2405-609X.3311
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