Citation

Sia, Boon Zhan and Boon, Wan Xin and Yap, Yoke Yee and Kumar, Shalini and Ng, Chong Han (2022) Prediction of the Effects of Nonsynonymous Variants on SARS-CoV-2 Proteins. F1000Research, 11. p. 9. ISSN 2046-1402

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Abstract

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 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.

Item Type:	Article
Uncontrolled Keywords:	SARS-CoV-2, nonsynonymous mutation, co-mutation, COVID-19
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Information Science and Technology (FIST)
Depositing User:	Ms Nurul Iqtiani Ahmad
Date Deposited:	01 Jul 2022 02:15
Last Modified:	01 Jul 2022 02:15
URII:	http://shdl.mmu.edu.my/id/eprint/10115

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