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...

Full description

Bibliographic Details
Main Authors: Xiaolong Lu, Yang Chen, Gong Zhang
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Computational and Structural Biotechnology Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S200103702300106X
_version_ 1797384127843926016
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
work_keys_str_mv AT xiaolonglu functionalevolutionofsarscov2spikeproteinmaintainingwidehostspectrumandenhancinginfectivityviasurfacechargeofspikeprotein
AT yangchen functionalevolutionofsarscov2spikeproteinmaintainingwidehostspectrumandenhancinginfectivityviasurfacechargeofspikeprotein
AT gongzhang functionalevolutionofsarscov2spikeproteinmaintainingwidehostspectrumandenhancinginfectivityviasurfacechargeofspikeprotein