Abstract
Background: SARS-CoV-2 virus is a highly transmissible pathogen that causes COVID-19. The outbreak originated in Wuhan, China in December 2019. A number of nonsynonymous mutations located at different SARS-CoV-2 proteins have been reported by multiple studies. However, there are limited computational studies on the biological impacts of these mutations on the structure and function of the proteins. Methods : In our study nonsynonymous mutations of the SARS-CoV-2 genome and their frequencies were identified from 30,229 sequences. Subsequently, the effects of the top 10 highest frequency nonsynonymous mutations of different SARS-CoV-2 proteins were analyzed using bioinformatics tools including co-mutation analysis, prediction of the protein structure stability and flexibility analysis, and prediction of the protein functions. Results: A total of 231 nonsynonymous mutations were identified from 30,229 SARS-CoV-2 genome sequences. The top 10 nonsynonymous mutations affecting nine amino acid residues were ORF1a nsp5 P108S, ORF1b nsp12 P323L and A423V, S protein N501Y and D614G, ORF3a Q57H, N protein P151L, R203K and G204R. Many nonsynonymous mutations showed a high concurrence ratio, suggesting these mutations may evolve together and interact functionally. Our result showed that ORF1a nsp5 P108S, ORF3a Q57H and N protein P151L mutations may be deleterious to the function of SARS-CoV-2 proteins. In addition, ORF1a nsp5 P108S and S protein D614G may destabilize the protein structures while S protein D614G may have a more open conformation compared to the wild type. Conclusion: The biological consequences of these nonsynonymous mutations of SARS-CoV-2 proteins should be further validated by in vivo and in vitro experimental studies in the future.
Keywords: COVID-19; SARS-CoV-2; co-mutation; nonsynonymous mutation.
【저자키워드】 COVID-19, SARS-CoV-2, co-mutation, nonsynonymous mutation., 【초록키워드】 Structure, Nsp12, Mutation, S protein, bioinformatics, SARS-CoV-2 virus, Proteins, in vitro, Protein, stability, pathogen, ORF3a, outbreak, N501Y, SARS-CoV-2 genome, Impact, Wuhan, N protein, D614G, protein structure, nsp5, in vivo, wild type, Amino acid, Frequency, Analysis, Nonsynonymous mutations, Q57H, Deleterious, SARS-CoV-2 proteins, SARS-CoV-2 genome sequences, ORF3, Computational study, P323L, ORF1b, ORF1a, functions, Multiple studies, SARS-CoV-2 protein, ORF1, computational studies, amino acid residue, Effect, consequence, Wuhan, China, nonsynonymous mutation, highest, analyzed, reported, addition, nine, cause, affecting, the SARS-CoV-2 genome, 【제목키워드】 prediction, Protein, SARS-CoV-2 strain, Effect, nonsynonymous variant,