Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein
The SARS-CoV-2 virus, which causes the COVID-19, is rapidly accumulating mutations to adapt to the hosts. We collected SARS-CoV-2 sequence data from the end of 2019 to January 2023 to analyze for their evolutionary features during the pandemic. We found that most of the SARS-CoV-2 genes are undergoi...
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Format: | Article |
Language: | English |
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Elsevier
2023-01-01
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Series: | Computational and Structural Biotechnology Journal |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S200103702300106X |
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author | Xiaolong Lu Yang Chen Gong Zhang |
author_facet | Xiaolong Lu Yang Chen Gong Zhang |
author_sort | Xiaolong Lu |
collection | DOAJ |
description | The SARS-CoV-2 virus, which causes the COVID-19, is rapidly accumulating mutations to adapt to the hosts. We collected SARS-CoV-2 sequence data from the end of 2019 to January 2023 to analyze for their evolutionary features during the pandemic. We found that most of the SARS-CoV-2 genes are undergoing negative purifying selection, while the spike protein gene (S-gene) is undergoing rapid positive selection. From the original strain to the alpha, delta and omicron variant types, the Ka/Ks of the S-gene increases, while the Ka/Ks within one variant type decreases over time. During the evolution, the codon usage did not evolve towards optimal translation and protein expression. In contrast, only S-gene mutations showed a remarkable trend on accumulating more positive charges. This facilitates the infection via binding human ACE2 for cell entry and binding furin for cleavage. Such a functional evolution emphasizes the survival strategy of SARS-CoV-2, and indicated new druggable target to contain the viral infection. The nearly fully positively-charged interaction surfaces indicated that the infectivity of SARS-CoV-2 virus may approach a limit. |
first_indexed | 2024-03-08T21:31:00Z |
format | Article |
id | doaj.art-4a6fdec6653f4a5180438c0420bb50aa |
institution | Directory Open Access Journal |
issn | 2001-0370 |
language | English |
last_indexed | 2024-03-08T21:31:00Z |
publishDate | 2023-01-01 |
publisher | Elsevier |
record_format | Article |
series | Computational and Structural Biotechnology Journal |
spelling | doaj.art-4a6fdec6653f4a5180438c0420bb50aa2023-12-21T07:31:11ZengElsevierComputational and Structural Biotechnology Journal2001-03702023-01-012120682074Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike proteinXiaolong Lu0Yang Chen1Gong Zhang2Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, Jinan University, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, Jinan University, Guangzhou, ChinaKey Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, Jinan University, Guangzhou, China; Chi-Biotech Co. Ltd., Shenzhen, China; Corresponding author at: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and MOE Key Laboratory of Tumor Molecular Biology, Institute of Life and Health Engineering, Jinan University, Guangzhou, China.The SARS-CoV-2 virus, which causes the COVID-19, is rapidly accumulating mutations to adapt to the hosts. We collected SARS-CoV-2 sequence data from the end of 2019 to January 2023 to analyze for their evolutionary features during the pandemic. We found that most of the SARS-CoV-2 genes are undergoing negative purifying selection, while the spike protein gene (S-gene) is undergoing rapid positive selection. From the original strain to the alpha, delta and omicron variant types, the Ka/Ks of the S-gene increases, while the Ka/Ks within one variant type decreases over time. During the evolution, the codon usage did not evolve towards optimal translation and protein expression. In contrast, only S-gene mutations showed a remarkable trend on accumulating more positive charges. This facilitates the infection via binding human ACE2 for cell entry and binding furin for cleavage. Such a functional evolution emphasizes the survival strategy of SARS-CoV-2, and indicated new druggable target to contain the viral infection. The nearly fully positively-charged interaction surfaces indicated that the infectivity of SARS-CoV-2 virus may approach a limit.http://www.sciencedirect.com/science/article/pii/S200103702300106XSARS-CoV-2Charge adaptationCodon usage adaptationKa/Ks evolutionSpike protein |
spellingShingle | Xiaolong Lu Yang Chen Gong Zhang Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein Computational and Structural Biotechnology Journal SARS-CoV-2 Charge adaptation Codon usage adaptation Ka/Ks evolution Spike protein |
title | Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein |
title_full | Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein |
title_fullStr | Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein |
title_full_unstemmed | Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein |
title_short | Functional evolution of SARS-CoV-2 spike protein: Maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein |
title_sort | functional evolution of sars cov 2 spike protein maintaining wide host spectrum and enhancing infectivity via surface charge of spike protein |
topic | SARS-CoV-2 Charge adaptation Codon usage adaptation Ka/Ks evolution Spike protein |
url | http://www.sciencedirect.com/science/article/pii/S200103702300106X |
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